Assessment of individual hand performance in box trainers compared to virtual reality trainers.

PubMed

Madan, Atul K; Frantzides, Constantine T; Shervin, Nina; Tebbit, Christopher L

2003-12-01

Training residents in laparoscopic skills is ideally initiated in an inanimate laboratory with both box trainers and virtual reality trainers. Virtual reality trainers have the ability to score individual hand performance although they are expensive. Here we compared the ability to assess dominant and nondominant hand performance in box trainers with virtual reality trainers. Medical students without laparoscopic experience were utilized in this study (n = 16). Each student performed tasks on the LTS 2000, an inanimate box trainer (placing pegs with both hands and transferring pegs from one hand to another), as well as a task on the MIST-VR, a virtual reality trainer (grasping a virtual object and placing it in a virtual receptable with alternating hands). A surgeon scored students for the inanimate box trainer exercises (time and errors) while the MIST-VR scored students (time, economy of movements, and errors for each hand). Statistical analysis included Pearson correlations. Errors and time for the one-handed tasks on the box trainer did not correlate with errors, time, or economy measured for each hand by the MIST-VR (r = 0.01 to 0.30; P = NS). Total errors on the virtual reality trainer did correlate with errors on transferring pege (r = 0.61; P < 0.05). Economy and time of both dominant and nondominant hand from the MIST-VR correlated with time of transferring pegs in the box trainer (r = 0.53 to 0.77; P < 0.05). While individual hand assessment by the box trainer during 2-handed tasks was related to assessment by the virtual reality trainer, individual hand assessment during 1-handed tasks did not correlate with the virtual reality trainer. Virtual reality trainers, such as the MIST-VR, allow assessment of individual hand skills which may lead to improved laparoscopic skill acquisition. It is difficult to assess individual hand performance with box trainers alone.

Visuospatial abilities and fine motor experiences influence acquisition and maintenance of fundamentals of laparoscopic surgery (FLS) task performance.

PubMed

Harrington, Cuan M; Dicker, Patrick; Traynor, Oscar; Kavanagh, Dara O

2018-05-18

Minimally invasive surgery poses a unique learning curve due to the requirement for non-intuitive psychomotor skills. The fundamentals of laparoscopic surgery (FLS) program trains and certifies residents in such skills. However, innate predictors of FLS performance and maintenance remain to be described. This single-centre observational study aimed to assess for candidate factors influencing the acquisition and maintenance of FLS performance amongst a surgically naïve cohort. Laparoscopically naïve medical students were recruited from pre-clinical university grades. Participants completed five visuospatial/psychomotor tests and a questionnaire surveying non-surgical experiences and personality traits. Individuals completed baseline assessments of FLS standard tasks followed by an intensive training course over week one and two on inanimate box trainers. A post-training assessment was performed in week three to evaluate acquisition. Participants were withdrawn from exposure and retested at four 1-month intervals to assess maintenance requirements. Forty-nine participants enrolled with 35 (71.4%) and 33 (67.3%) completing acquisition and maintenance phases, respectively. Mean age of participants was 19.3 (± 1.2) years with 68.6% female predominance. Participants demonstrated significant improvements in all five tasks during the acquisition (p < 0.05) period and maintenance of skills with task exposure at 1-month intervals. Significant predictors of skill acquisition included: card rotations for intracorporeal knot (p = 0.027) and combined tasks (p = 0.028) and cube comparisons for extracorporeal knot (p = 0.040). During skill maintenance: Card rotations predicted performance across all tasks (p < 0.05), Cube comparisons for tasks 1/2/4/5 (p < 0.05), PicSOR for peg transfer (p = 0.017) and grooved pegboard for peg transfer (p = 0.023) and ligating-loop (p = 0.038) tasks. Musical instrument experience demonstrated associations with skill acquisition in peg transfer (p = 0.042) and intracorporeal knot (p = 0.034) while video gaming predicted performance in these tasks (p < 0.05) during the maintenance phase. A sporting background or competitive personality did not influence skill performance. Multiple visuospatial abilities and non-surgical experiences positively influenced FLS performance during skill acquisition and/or maintenance. Further consideration to these individual factors may facilitate selection of more technically adaptable surgical residents.

A randomized controlled study to establish the effect of articulating instruments on performance in single-incision laparoscopic surgery.

PubMed

Corker, Harry P; Singh, Pritam; Sodergren, Mikael H; Balaji, Sathyan; Kwasnicki, Richard M; Darzi, Ara W; Paraskeva, Paraskevas

2015-01-01

In single-incision laparoscopic surgery (SILS), operating through 1 incision presents ergonomic challenges. No consensus exists on whether articulating instruments (ARTs) may help. This study evaluated their effect on simulated SILS, hypothesizing that they would affect performance and workload. Surgeons were randomized to 2 straight instruments (STRs), 1 ART and 1 STR, or 2 ARTs. After baseline testing, 25 repetitions of the Fundamentals of Laparoscopic Surgery (FLS) peg-transfer (PEG) task and 5 repetitions of the short-hand for the FLS pattern-cutting task (CIRCLE) were performed. Primary outcomes were maximum FLS PEG scores, CIRCLE times and errors, and Imperial College Surgical Assessment Device hand motion analysis. National Aeronautics and Space Administration (NASA) Raw Task Load Index (RTLX) questionnaires evaluated a secondary outcome--workload. The trial took place in a simulated operating theater within the Academic Surgical Unit at St Mary's Hospital, London, UK. Eligible surgeons had completed at least 5 laparoscopic cases as a primary operator. Surgeons were stratified by laparoscopic experience into intermediate (less than 25 previous procedures as primary operator) or advanced (25 procedures or more). A total of 21 surgeons were recruited and randomized; 7 of them to each instrument combination group. All surgeons completed PEG, and 5 from each group completed CIRCLE. Groups' baseline PEG scores were similar (p = 0.625). STR-ART achieved higher maximum PEG scores than STR or ART did (median = 236 vs 198 vs 193, respectively, p = 0.002). Fastest CIRCLE times were similar (median = 190s vs 130s vs 186s, p = 0.129) as were minimum errors (median = 1 vs 2 vs 3, p = 0.101). For PEG, Imperial College Surgical Assessment Device demonstrated similar total path lengths (median = 12.3m vs 12.3m vs 16.0m, p = 0.545) and total numbers of movements (median = 89.6 vs 86.4 vs 171, p = 0.080). Groups' NASA Raw Task Load Index scores were similar (p = 0.708). Combining 1 STR and 1 ART improved SILS performance in the PEG task. Therefore, this may be the optimum instrument configuration for use within some clinical SILS applications. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Impaired laparoscopic performance of novice surgeons due to phone call distraction: a single-centre, prospective study.

PubMed

Yang, Cui; Heinze, Julia; Helmert, Jens; Weitz, Juergen; Reissfelder, Christoph; Mees, Soeren Torge

2017-12-01

Distractions such as phone calls during laparoscopic surgery play an important role in many operating rooms. The aim of this single-centre, prospective study was to assess if laparoscopic performance is impaired by intraoperative phone calls in novice surgeons. From October 2015 to June 2016, 30 novice surgeons (medical students) underwent a laparoscopic surgery training curriculum including two validated tasks (peg transfer, precision cutting) until achieving a defined level of proficiency. For testing, participants were required to perform these tasks under three conditions: no distraction (control) and two standardised distractions in terms of phone calls requiring response (mild and strong distraction). Task performance was evaluated by analysing time and accuracy of the tasks and response of the phone call. In peg transfer (easy task), mild distraction did not worsen the performance significantly, while strong distraction was linked to error and inefficiency with significantly deteriorated performance (P < 0.05). Precision cutting (difficult task) was not slowed down by mild distraction, but surgical and cognitive errors were significantly increased when participants were distracted (P < 0.05). Compared to mild distraction, participants reported a more severe subjective disturbance when they were diverted by strong distraction (P < 0.05). Our data reveals that phone call distractions result in impaired laparoscopic performance under certain circumstances. To ensure patient safety, phone calls should be avoided as far as possible in operating rooms.

The effect of ergonomic laparoscopic tool handle design on performance and efficiency.

PubMed

Tung, Kryztopher D; Shorti, Rami M; Downey, Earl C; Bloswick, Donald S; Merryweather, Andrew S

2015-09-01

Many factors can affect a surgeon's performance in the operating room; these may include surgeon comfort, ergonomics of tool handle design, and fatigue. A laparoscopic tool handle designed with ergonomic considerations (pistol grip) was tested against a current market tool with a traditional pinch grip handle. The goal of this study is to quantify the impact ergonomic design considerations which have on surgeon performance. We hypothesized that there will be measurable differences between the efficiency while performing FLS surgical trainer tasks when using both tool handle designs in three categories: time to completion, technical skill, and subjective user ratings. The pistol grip incorporates an ergonomic interface intended to reduce contact stress points on the hand and fingers, promote a more neutral operating wrist posture, and reduce hand tremor and fatigue. The traditional pinch grip is a laparoscopic tool developed by Stryker Inc. widely used during minimal invasive surgery. Twenty-three (13 M, 10 F) participants with no existing upper extremity musculoskeletal disorders or experience performing laparoscopic procedures were selected to perform in this study. During a training session prior to testing, participants performed practice trials in a SAGES FLS trainer with both tools. During data collection, participants performed three evaluation tasks using both handle designs (order was randomized, and each trial completed three times). The tasks consisted of FLS peg transfer, cutting, and suturing tasks. Feedback from test participants indicated that they significantly preferred the ergonomic pistol grip in every category (p < 0.05); most notably, participants experienced greater degrees of discomfort in their hands after using the pinch grip tool. Furthermore, participants completed cutting and peg transfer tasks in a shorter time duration (p < 0.05) with the pistol grip than with the pinch grip design; there was no significant difference between completion times for the suturing task. Finally, there was no significant interaction between tool type and errors made during trials. There was a significant preference for as well as lower pain experienced during use of the pistol grip tool as seen from the survey feedback. Both evaluation tasks (cutting and peg transfer) were also completed significantly faster with the pistol grip tool. Finally, due to the high degree of variability in the error data, it was not possible to draw any meaningful conclusions about the effect of tool design on the number or degree of errors made.

Characterizing the Learning Curve of the VBLaST-PT© (Virtual Basic Laparoscopic Skill Trainer)

PubMed Central

Zhang, Likun; Sankaranarayanan, Ganesh; Arikatla, Venkata Sreekanth; Ahn, Woojin; Grosdemouge, Cristol; Rideout, Jesse M.; Epstein, Scott K.; De, Suvranu; Schwaitzberg, Steven D.; Jones, Daniel B.; Cao, Caroline G.L.

2013-01-01

Background and study aim Mastering laparoscopic surgical skills requires considerable time and effort. The Virtual Basic Laparoscopic Skill Trainer (VBLaST-PT©) is being developed as a computerized version of the peg transfer task of the Fundamentals of Laparoscopic Surgery (FLS) system using virtual reality technology. We assessed the learning curve of trainees on the VBLaST-PT© using the cumulative summation (CUSUM) method and compared them with those on the FLS to establish convergent validity for the VBLaST-PT©. Methods Eighteen medical students from were assigned randomly to one of three groups: control, VBLaST-training and FLS-training. The VBLaST and the FLS groups performed a total of 150 trials of the peg-transfer task over a three week period, five days a week. Their CUSUM scores were computed based on pre-defined performance criteria (junior, intermediate and senior levels). Results Of the six subjects in the VBLaST-training group, five achieved at least the “junior” level, three achieved the “intermediate” level and one achieved the “senior” level of performance criterion by the end of the 150 trials. In comparison, for the FLS group, three students achieved the “senior” criterion and all six students achieved the “intermediate” and “junior” criteria by the 150th trials. Both the VBLaST-PT© and the FLS systems showed significant skill improvement and retention, albeit with system specificity as measured by transfer of learning in the retention test: The VBLaST-trained group performed better on the VBLaST-PT© than on FLS (p=0.003), while the FLS-trained group performed better on the FLS than on VBLaST-PT© (p=0.002). Conclusion We characterized the learning curve for a virtual peg transfer task on the VBLaST-PT© and compared it with the FLS using CUSUM analysis. Subjects in both training groups showed significant improvement in skill performance, but the transfer of training between systems was not significant. PMID:23572217

Impact of Super Monkey Ball and Underground video games on basic and advanced laparoscopic skill training.

PubMed

Rosser, James C; Liu, Xinwei; Jacobs, Charles; Choi, Katherine Mia; Jalink, Maarten B; Ten Cate Hoedemaker, Henk O

2017-04-01

This abstract profiles the comparison of correlations between previously validated Super Monkey Ball (SMB) and recently introduced Underground (U) video game on the Nintendo Wii U to multiple validated tasks used for developing basic and advanced laparoscopic skills. Sixty-eight participants, 53 residents and 15 attending surgeons, performed the Top Gun Pea Drop, FLS Peg Pass, intracorporeal suturing, and two video games (SMB and U). SMB is an over-the-counter game, and U was formulated for laparoscopic skill training. Spearman's rank correlations were performed looking at performance comparing the three validated laparoscopic training tasks, and SMB/U. The SMB score had a moderate correlation with intracorporeal suturing (ρ = 0.39, p < 0.01), and the final score involving all three tasks (ρ = 0.39, p < 0.01), but low correlations with Pea Drop Drill and FLS Peg Transfer (ρ = 0.11, 0.18, p < 0.01). The U score had a small correlation with intracorporeal suturing and final score (ρ = 0.09, 0.13, p < 0.01). However, there were correlations between U score and Pea Drop Drill, and FLS Peg Transfer (ρ = 0.24, 0.27, p < 0.01, respectively). In this study, SMB had a very significant correlation with intracorporeal suturing. U demonstrated more of a correlation with basic skills. At this point, our conclusion would be that both are effective for laparoscopic skill training, and they should be used in tandem rather than alone.

Bringing the skills laboratory home: an affordable webcam-based personal trainer for developing laparoscopic skills.

PubMed

Kobayashi, Sow Alfred; Jamshidi, Ramin; O'Sullivan, Patricia; Palmer, Barnard; Hirose, Shinjiro; Stewart, Lygia; Kim, Edward Hyung

2011-01-01

The purpose of this work was to develop a more flexible system of laparoscopic surgery training with demonstrated effectiveness and construct validity. A personal, portable, durable laparoscopic trainer can be designed at low cost. The evaluation of expert surgeons on this device will reveal technical superiority over novices. With practice, novice surgeons can improve their performance significantly as measured by scores derived from performing skills with this training device. Prospective trial with observation and intervention components. The first aspect was observational comparison of novice and expert performance. The second was a prospective static-group comparison with pretest/posttest single-sample design. Tertiary-care academic medical center with affiliated general surgery residency. A total of 21 junior surgical residents and 5 experienced operators. Performance was assessed by the 5 tasks in the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS): pegboard transfer, pattern cutting, placement of ligating loop, extracorporeal knotting, and intracorporeal knotting. Each task was assessed for accuracy and speed. Expert surgeons scored significantly higher than novices on total score and 4 of the 5 MISTELS tasks (peg transfer, pattern cut, extracorporeal knot, and intracorporeal knot). After 4 months of home-based training, the novices improved in total score and 3 of the 5 tasks (peg transfer, pattern cut, and extracorporeal knot). A low-cost personal laparoscopic training device can be built by individual residents. With their use, residents can significantly improve performance in important surgical skills. Evaluation of the system supports its validity. Copyright © 2011 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Construct validity of individual and summary performance metrics associated with a computer-based laparoscopic simulator.

PubMed

Rivard, Justin D; Vergis, Ashley S; Unger, Bertram J; Hardy, Krista M; Andrew, Chris G; Gillman, Lawrence M; Park, Jason

2014-06-01

Computer-based surgical simulators capture a multitude of metrics based on different aspects of performance, such as speed, accuracy, and movement efficiency. However, without rigorous assessment, it may be unclear whether all, some, or none of these metrics actually reflect technical skill, which can compromise educational efforts on these simulators. We assessed the construct validity of individual performance metrics on the LapVR simulator (Immersion Medical, San Jose, CA, USA) and used these data to create task-specific summary metrics. Medical students with no prior laparoscopic experience (novices, N = 12), junior surgical residents with some laparoscopic experience (intermediates, N = 12), and experienced surgeons (experts, N = 11) all completed three repetitions of four LapVR simulator tasks. The tasks included three basic skills (peg transfer, cutting, clipping) and one procedural skill (adhesiolysis). We selected 36 individual metrics on the four tasks that assessed six different aspects of performance, including speed, motion path length, respect for tissue, accuracy, task-specific errors, and successful task completion. Four of seven individual metrics assessed for peg transfer, six of ten metrics for cutting, four of nine metrics for clipping, and three of ten metrics for adhesiolysis discriminated between experience levels. Time and motion path length were significant on all four tasks. We used the validated individual metrics to create summary equations for each task, which successfully distinguished between the different experience levels. Educators should maintain some skepticism when reviewing the plethora of metrics captured by computer-based simulators, as some but not all are valid. We showed the construct validity of a limited number of individual metrics and developed summary metrics for the LapVR. The summary metrics provide a succinct way of assessing skill with a single metric for each task, but require further validation.

The impact of heat stress on operative performance and cognitive function during simulated laparoscopic operative tasks.

PubMed

Berg, Regan J; Inaba, Kenji; Sullivan, Maura; Okoye, Obi; Siboni, Stefano; Minneti, Michael; Teixeira, Pedro G; Demetriades, Demetrios

2015-01-01

Increasing ambient temperature to prevent intraoperative patient hypothermia remains widely advocated despite unconvincing evidence of efficacy. Heat stress is associated with decreased cognitive and psychomotor performance across multiple tasks but remains unexamined in an operative context. We assessed the impact of increased ambient temperature on laparoscopic operative performance and surgeon cognitive stress. Forty-two performance measures were obtained from 21 surgery trainees participating in the counter-balanced, within-subjects study protocol. Operative performance was evaluated with adaptations of the validated, peg-transfer, and intracorporeal knot-tying tasks from the Fundamentals of Laparoscopic Surgery program. Participants trained to proficiency before enrollment. Task performance was measured at two ambient temperatures, 19 and 26°C (66 and 79°F). Participants were randomly counterbalanced to initial hot or cold exposure before crossing over to the alternate environment. Cognitive stress was measured using the validated Surgical Task Load Index (SURG-TLX). No differences in performance of the peg-transfer and intracorporeal knot-tying tasks were seen across ambient conditions. Assessed via use of the six bipolar scales of the SURG-TLX, we found differences in task workload between the hot and cold conditions in the areas of physical demands (hot 10 [3-12], cold 5 [2.5-9], P = .013) and distractions (hot 8 [3.5-15.5], cold 3 [1.5-5.5], P = .001). Participant perception of distraction remained greater in the hot condition on full scoring of the SURG-TLX. Increasing ambient temperature to levels advocated for prevention of intraoperative hypothermia does not greatly decrease technical performance in short operative tasks. Surgeons, however, do report increased perceptions of distraction and physical demand. The impact of these findings on performance and outcomes during longer operative procedures remains unclear. Copyright © 2015 Elsevier Inc. All rights reserved.

Is Single-Port Laparoscopy More Precise and Faster with the Robot?

PubMed

Fransen, Sofie A F; van den Bos, Jacqueline; Stassen, Laurents P S; Bouvy, Nicole D

2016-11-01

Single-port laparoscopy is a step forward toward nearly scar less surgery. Concern has been raised that single-incision laparoscopic surgery (SILS) is technically more challenging because of the lack of triangulation and the clashing of instruments. Robotic single-incision laparoscopic surgery (RSILS) in chopstick setting might overcome these problems. This study evaluated the outcome in time and errors of two tasks of the Fundamentals of Laparoscopic Surgery on a dry platform, in two settings: SILS versus RSILS. Nine experienced laparoscopic surgeons performed two tasks: peg transfer and a suturing task, on a standard box trainer. All participants practiced each task three times in both settings: SILS and a RSILS setting. The assessment scores (time and errors) were recorded. For the first task of peg transfer, RSILS was significantly better in time (124 versus 230 seconds, P = .0004) and errors (0.80 errors versus 2.60 errors, P = .024) at the first run, compared to the SILS setting. At the third and final run, RSILS still proved to be significantly better in errors (0.10 errors versus 0.80 errors, P = .025) compared to the SILS group. RSILS was faster in the third run, but not significant (116 versus 157 seconds, P = .08). For the second task, a suturing task, only 3 participants of the SILS group were able to perform this task within the set time frame of 600 seconds. There was no significant difference in time in the three runs between SILS and RSILS for the 3 participants that fulfilled both tasks within the 600 seconds. This study shows that robotic single-port surgery seems easier, faster, and more precise to perform basis tasks of the Fundamentals of laparoscopic surgery. For the more complex task of suturing, only the single-port robotic setting enabled all participants to fulfill this task, within the set time frame.

Haptic feedback for virtual assembly

NASA Astrophysics Data System (ADS)

Luecke, Greg R.; Zafer, Naci

1998-12-01

Assembly operations require high speed and precision with low cost. The manufacturing industry has recently turned attenuation to the possibility of investigating assembly procedures using graphical display of CAD parts. For these tasks, some sort of feedback to the person is invaluable in providing a real sense of interaction with virtual parts. This research develops the use of a commercial assembly robot as the haptic display in such tasks. For demonstration, a peg-hole insertion task is studied. Kane's Method is employed to derive the dynamics of the peg and the contact motions between the peg and the hole. A handle modeled as a cylindrical peg is attached to the end effector of a PUMA 560 robotic arm. The arm is handle modeled as a cylindrical peg is attached to the end effector of a PUMA 560 robotic arm. The arm is equipped with a six axis force/torque transducer. The use grabs the handle and the user-applied forces are recorded. A 300 MHz Pentium computer is used to simulate the dynamics of the virtual peg and its interactions as it is inserted in the virtual hole. The computed torque control is then employed to exert the full dynamics of the task to the user hand. Visual feedback is also incorporated to help the user in the process of inserting the peg into the hole. Experimental results are presented to show several contact configurations for this virtually simulated task.

Establishing the minimal number of virtual reality simulator training sessions necessary to develop basic laparoscopic skills competence: evaluation of the learning curve.

PubMed

Duarte, Ricardo Jordão; Cury, José; Oliveira, Luis Carlos Neves; Srougi, Miguel

2013-01-01

Medical literature is scarce on information to define a basic skills training program for laparoscopic surgery (peg and transferring, cutting, clipping). The aim of this study was to determine the minimal number of simulator sessions of basic laparoscopic tasks necessary to elaborate an optimal virtual reality training curriculum. Eleven medical students with no previous laparoscopic experience were spontaneously enrolled. They were submitted to simulator training sessions starting at level 1 (Immersion Lap VR, San Jose, CA), including sequentially camera handling, peg and transfer, clipping and cutting. Each student trained twice a week until 10 sessions were completed. The score indexes were registered and analyzed. The total of errors of the evaluation sequences (camera, peg and transfer, clipping and cutting) were computed and thereafter, they were correlated to the total of items evaluated in each step, resulting in a success percent ratio for each student for each set of each completed session. Thereafter, we computed the cumulative success rate in 10 sessions, obtaining an analysis of the learning process. By non-linear regression the learning curve was analyzed. By the non-linear regression method the learning curve was analyzed and a r2 = 0.73 (p < 0.001) was obtained, being necessary 4.26 (∼five sessions) to reach the plateau of 80% of the estimated acquired knowledge, being that 100% of the students have reached this level of skills. From the fifth session till the 10th, the gain of knowledge was not significant, although some students reached 96% of the expected improvement. This study revealed that after five simulator training sequential sessions the students' learning curve reaches a plateau. The forward sessions in the same difficult level do not promote any improvement in laparoscopic basic surgical skills, and the students should be introduced to a more difficult training tasks level.

A master manipulator with a remote-center-of-motion kinematic structure for a minimally invasive robotic surgical system.

PubMed

Lee, Hyunyoung; Cheon, Byungsik; Hwang, Minho; Kang, Donghoon; Kwon, Dong-Soo

2018-02-01

In robotic surgical systems, commercial master devices have limitations owing to insufficient workspace and lack of intuitiveness. To overcome these limitations, a remote-center-of-motion (RCM) master manipulator was proposed. The feasibility of the proposed RCM structure was evaluated through kinematic analysis using a conventional serial structure. Two performance comparison experiments (peg transfer task and objective transfer task) were conducted for the developed master and Phantom Omni. The kinematic analysis results showed that compared with the serial structure, the proposed RCM structure has better performance in terms of design efficiency (19%) and workspace quality (59.08%). Further, in comparison with Phantom Omni, the developed master significantly increased task efficiency and significantly decreased workload in both experiments. The comparatively better performance in terms of intuitiveness, design efficiency, and operability of the proposed master for a robotic system for minimally invasive surgery was confirmed through kinematic and experimental analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Do laparoscopic skills transfer to robotic surgery?

PubMed

Panait, Lucian; Shetty, Shohan; Shewokis, Patricia A; Sanchez, Juan A

2014-03-01

Identifying the set of skills that can transfer from laparoscopic to robotic surgery is an important consideration in designing optimal training curricula. We tested the degree to which laparoscopic skills transfer to a robotic platform. Fourteen medical students and 14 surgery residents with no previous robotic but varying degrees of laparoscopic experience were studied. Three fundamentals of laparoscopic surgery tasks were used on the laparoscopic box trainer and then the da Vinci robot: peg transfer (PT), circle cutting (CC), and intracorporeal suturing (IS). A questionnaire was administered for assessing subjects' comfort level with each task. Standard fundamentals of laparoscopic surgery scoring metric were used and higher scores indicate a superior performance. For the group, PT and CC scores were similar between robotic and laparoscopic modalities (90 versus 90 and 52 versus 47; P > 0.05). However, for the advanced IS task, robotic-IS scores were significantly higher than laparoscopic-IS (80 versus 53; P < 0.001). Subgroup analysis of senior residents revealed a lower robotic-PT score when compared with laparoscopic-PT (92 versus 105; P < 0.05). Scores for CC and IS were similar in this subgroup (64 ± 9 versus 69 ± 15 and 95 ± 3 versus 92 ± 10; P > 0.05). The robot was favored over laparoscopy for all drills (PT, 66.7%; CC, 88.9%; IS, 94.4%). For simple tasks, participants with preexisting skills perform worse with the robot. However, with increasing task difficulty, robotic performance is equal or better than laparoscopy. Laparoscopic skills appear to readily transfer to a robotic platform, and difficult tasks such as IS are actually enhanced, even in subjects naive to the technology. Copyright © 2014 Elsevier Inc. All rights reserved.

COMPARISON OF LAPAROSCOPIC SKILLS PERFORMANCE USING SINGLE-SITE ACCESS (SSA) DEVICES VS. AN INDEPENDENT-PORT SSA APPROACH

PubMed Central

Schill, Matthew R.; Varela, J. Esteban; Frisella, Margaret M.; Brunt, L. Michael

2015-01-01

Background We compared performance of validated laparoscopic tasks on four commercially available single site access (SSA) access devices (AD) versus an independent port (IP) SSA set-up. Methods A prospective, randomized comparison of laparoscopic skills performance on four AD (GelPOINT™, SILS™ Port, SSL Access System™, TriPort™) and one IP SSA set-up was conducted. Eighteen medical students (2nd–4th year), four surgical residents, and five attending surgeons were trained to proficiency in multi-port laparoscopy using four laparoscopic drills (peg transfer, bean drop, pattern cutting, extracorporeal suturing) in a laparoscopic trainer box. Drills were then performed in random order on each IP-SSA and AD-SSA set-up using straight laparoscopic instruments. Repetitions were timed and errors recorded. Data are mean ± SD, and statistical analysis was by two-way ANOVA with Tukey HSD post-hoc tests. Results Attending surgeons had significantly faster total task times than residents or students (p< 0.001), but the difference between residents and students was NS. Pair-wise comparisons revealed significantly faster total task times for the IP-SSA set-up compared to all four AD-SSA’s within the student group only (p<0.05). Total task times for residents and attending surgeons showed a similar profile, but the differences were NS. When data for the three groups was combined, the total task time was less for the IP-SSA set-up than for each of the four AD-SSA set-ups (p < 0.001). Similarly,, the IP-SSA set-up was significantly faster than 3 of 4 AD-SSA set-ups for peg transfer, 3 of 4 for pattern cutting, and 2 of 4 for suturing. No significant differences in error rates between IP-SSA and AD-SSA set-ups were detected. Conclusions When compared to an IP-SSA laparoscopic set-up, single site access devices are associated with longer task performance times in a trainer box model, independent of level of training. Task performance was similar across different SSA devices. PMID:21993938

Bilateral transfer phenomenon: A functional magnetic resonance imaging pilot study of healthy subjects.

PubMed

Uggetti, Carla; Ausenda, Carlo D; Squarza, Silvia; Cadioli, Marcello; Grimoldi, Ludovico; Cerri, Cesare; Cariati, Maurizio

2016-08-01

The bilateral transfer of a motor skill is a physiological phenomenon: the development of a motor skill with one hand can trigger the development of the same ability of the other hand. The purpose of this study was to verify whether bilateral transfer is associated with a specific brain activation pattern using functional magnetic resonance imaging (fMRI). The motor task was implemented as the execution of the Nine Hole Peg Test. Fifteen healthy subjects (10 right-handers and five left-handers) underwent two identical fMRI runs performing the motor task with the non-dominant hand. Between the first and the second run, each subject was intensively trained for five minutes to perform the same motor task with the dominant hand. Comparing the two functional scans across the pool of subjects, a change of the motor activation pattern was observed. In particular, we observed, in the second run, a change in the activation pattern both in the cerebellum and in the cerebral cortex. We found activations in cortical areas involved in somatosensory integration, areas involved in procedural memory. Our study shows, in a small group of healthy subjects, the modification of the fMRI activation pathway of a motor task performed by the non-dominant hand after intensive exercise performing the same task with the dominant hand. © The Author(s) 2016.

Visual-perceptual mismatch in robotic surgery.

PubMed

Abiri, Ahmad; Tao, Anna; LaRocca, Meg; Guan, Xingmin; Askari, Syed J; Bisley, James W; Dutson, Erik P; Grundfest, Warren S

2017-08-01

The principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator. We asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded. Compared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p < 0.001). Additionally, it was observed that addition of tactile feedback helps reduce the negative effects of visual-perceptual mismatch in some cases. Grip force data recorded from grasper-mounted sensors showed no difference between the different groups. The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat

PubMed Central

Grous, Lauren Conova; Vernengo, Jennifer; Jin, Ying; Himes, B. Timothy; Shumsky, Jed S.; Fischer, Itzhak; Lowman, Anthony

2016-01-01

Object In a follow-up study to their prior work, the authors evaluated a novel delivery system for a previously established treatment for spinal cord injury (SCI), based on a poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with a polyethylene glycol (PEG) injectable scaffold. The primary aim of this work was to assess the recovery of both spontaneous and skilled forelimb function following a cervical dorsolateral funiculotomy in the rat. This injury ablates the rubrospinal tract (RST) but spares the dorsal and ventral corticospinal tract and can severely impair reaching and grasping abilities. Methods Animals received an implant of either PNIPAAm-g-PEG or PNIPAAm-g-PEG + brain-derived neurotrophic factor (BDNF). The single-pellet reach-to-grasp task and the staircase-reaching task were used to assess skilled motor function associated with reaching and grasping abilities, and the cylinder task was used to assess spontaneous motor function, both before and after injury. Results Because BDNF can stimulate regenerating RST axons, the authors showed that animals receiving an implant of PNIPAAm-g-PEG with codissolved BDNF had an increased recovery rate of fine motor function when compared with a control group (PNIPAAm-g-PEG only) on both a staircase-reaching task at 4 and 8 weeks post-SCI and on a single-pellet reach-to-grasp task at 5 weeks post-SCI. In addition, spontaneous motor function, as measured in the cylinder test, recovered to preinjury values in animals receiving PNIPAAm-g-PEG + BDNF. Fluorescence immunochemistry indicated the presence of both regenerating axons and BDA-labeled fibers growing up to or within the host-graft interface in animals receiving PNIPAAm-g-PEG + BDNF. Conclusions Based on their results, the authors suggest that BDNF delivered by the scaffold promoted the growth of RST axons into the lesion, which may have contributed in part to the increased recovery rate. PMID:23581453

SAGES Mini Med School: inspiring high school students through exposure to the field of surgery.

PubMed

Rosser, James C; Legare, Timothy B; Jacobs, Charles; Choi, Katherine M; Fleming, Jeffrey P; Nakagiri, Jamie

2018-04-02

The SAGES Mini Med School (SMMS) was designed to expose high school students to the field of surgery through mentoring, knowledge transfer, and hands-on experience with simulation. The objective of this paper is to profile the evolutionary development, performance metrics, and satisfaction queries of this innovative effort. Sixty-one high school students, grades 9-12, took part in the (SMMS) program during the 2015 SAGES Annual Congress. The students completed a surgical skills lab session where they attempted tasks associated with the development of open surgical and laparoscopic skills. The lab included a warm-up with the validated Super Monkey Ball video game, Top Gun Pea Drop task, FLS Peg Transfer task, open knot tying station, and open instrument tie station. The following are the results of the surgical skills lab. For the Super Monkey Ball task, 60 students participated with an average score of 73.0 s (SD = 53.9; range 59.1-87.0; median = 74). Sixty students participated in the Surgeons Knot and Pea Drop tasks with average times of 26.6 s (SD = 19.3; range 21.7-31.6; median = 21.0) and 113.8 s (SD = 65.9; range 96.6-131.0; median = 101.0), respectively. Sixty students participated in the Instrument Tie and 56 students participated in the Peg Transfer stations with average times of 51.7 s (SD = 34.5; range 42.8-60.6; median = 39.5) and 173.1 s (SD = 25.0; range 166.4-179.8; median = 180.0), respectively. 51 (83.6%) agreed that the Mini Med School made them more likely to consider a career in medicine. When asked if the program made them more likely to consider a career in surgery 42 (68.8%) agreed. All 61 respondents (100%) said that they would recommend the program to others. The SMMS program showed that the students had an excellent aptitude for the performance of validated surgical subtasks with high satisfaction, and increased consideration of a career in medicine/surgery. Long-term studies are needed to evaluate the impact on workforce recruitment.

Laparoscopic and robotic skills are transferable in a simulation setting: a randomized controlled trial.

PubMed

Thomaier, Lauren; Orlando, Megan; Abernethy, Melinda; Paka, Chandhana; Chen, Chi Chiung Grace

2017-08-01

Although surgical simulation provides an effective supplement to traditional training, it is not known whether skills are transferable between minimally invasive surgical modalities. The purpose of this study was to assess the transferability of skills between minimally invasive surgical simulation platforms among simulation-naïve participants. Forty simulation-naïve medical students were enrolled in this randomized single-blinded controlled trial. Participants completed a baseline evaluation on laparoscopic (Fundamentals of Laparoscopic Surgery Program, Los Angeles, CA) and robotic (dV-Trainer, Mimic, Seattle, WA) simulation peg transfer tasks. Participants were then randomized to perform a practice session on either the robotic (N = 20) or laparoscopic (N = 20) simulator. Two blinded, expert minimally invasive surgeons evaluated participants before and after training using a modified previously validated subjective global rating scale. Objective measures including time to task completion and Mimic dV-Trainer motion metrics were also recorded. At baseline, there were no significant differences between the training groups as measured by objective and subjective measures for either simulation task. After training, participants randomized to the laparoscopic practice group completed the laparoscopic task faster (p < 0.003) and with higher global rating scale scores (p < 0.001) than the robotic group. Robotic-trained participants performed the robotic task faster (p < 0.001), with improved economy of motion (p < 0.001), and with higher global rating scale scores (p = 0.006) than the laparoscopic group. The robotic practice group also demonstrated significantly improved performance on the laparoscopic task (p = 0.02). Laparoscopic-trained participants also improved their robotic performance (p = 0.02), though the robotic group had a higher percent improvement on the robotic task (p = 0.037). Skills acquired through practice on either laparoscopic or robotic simulation platforms appear to be transferable between modalities. However, participants demonstrate superior skill in the modality in which they specifically train.

Transfer of motor skill learning from the healthy hand to the paretic hand in stroke patients: a randomized controlled trial.

PubMed

Ausenda, C; Carnovali, M

2011-09-01

Bilateral transfer of a motor skill is a phenomenon based on the observation that the performance of a skill with one hand can "teach" the same skill to the other hand. In this study the ability of bilateral transfer to facilitate the motor skill of the paretic hand in patients that suffered a stroke was tested. In a randomized controlled trial subjects were randomly assigned to either the test group or the control group. The experiment was performed in a general hospital rehabilitation facility for inpatients and outpatients. We studied 20 outpatients, who had their first stroke episode characterized by a brain lesion to a single hemisphere, at the end of their rehabilitation treatment. The criteria used for the selection were based on a physical examination, the time elapsed from the stroke and cognitive requirements. The experiment consisted in training the healthy hand of each patient from the test group to execute the nine hole peg test 10 times a day, for three consecutive days, and then test the paretic hand with the same test and with bimanual tasks. The control group was not trained but went through the same analysis. The homogeneity of the two groups has been proven. In the test group we found that the execution speed of the nine hole peg test with the paretic hand, after training the healthy hand, was on average 22.6% faster than the value recorded at baseline. The training had a positive effect on the execution of bimanual tasks. Meanwhile, no significant difference was found in the control group. This is the first evidence that bilateral transfer of motor skills is present in patients that suffered a stroke, and that it improves the ability of the affected hand. This observation could open the way to the development of a new approach for the rehabilitation of stroke patients.

Introducing Students to Surface Modification and Phase Transfer of Nanoparticles with a Laboratory Experiment

ERIC Educational Resources Information Center

Alkilany, Alaaldin M.; Mansour, Sara; Amro, Hamza M.; Pelaz, Beatriz; Soliman, Mahmoud G.; Hinman, Joshua G.; Dennison, Jordan M.; Parak, Wolfgang J.; Murphy, Catherine J.

2017-01-01

A simple, reliable, and cost-effective experiment is presented in which students synthesized citrate-capped gold nanoparticles (GNPs), functionalized them with poly(ethylene glycol) (PEG), and transferred the PEG-GNPs from water to the organic phase dichloromethane. The experiment introduces students to nanotechnology with foci on important…

Two measures of performance in a peg-in-hole manipulation task with force feedback

NASA Technical Reports Server (NTRS)

Hill, J. W.

1977-01-01

The results are described from two manipulators on a peg-in-hole task, which is part of a continued effort to develop models for human performance with remote manipulators. Task difficulty is varied by changing the diameter of the peg to be inserted in a 50 mm diameter hole. An automatic measuring system records the distance between the tool being held by the manipulator and the receptacle into which it is to be inserted. The data from repeated insertions are processed by computer to determine task times, accumulated distances, and trajectories. Experiments with both the MA-11 cable-connected master-slave manipulator common to hot cell work and the MA-23 servo-controlled manipulator (with and without force feedback) are described. Comparison of these results with previous results of the Ames Manipulator shows that force feedback provides a consistent advantage.

A PEG/copper(i) halide cluster as an eco-friendly catalytic system for C-N bond formation.

PubMed

Li, Cheng-An; Ji, Wei; Qu, Jian; Jing, Su; Gao, Fei; Zhu, Dun-Ru

2018-05-22

The catalytic activities of eight copper(i) halide clusters assembled from copper(i) halide and ferrocenyltelluroethers, 1-8, were investigated in C-N formation under various conditions. A catalytic procedure using poly(ethylene glycol) (PEG-400) as a greener alternative organic solvent has been developed. The PEG-400/5 system can achieve 99% targeted yield with a mild reaction temperature and short reaction time. After the isolation of the products by extraction with diethyl ether, this PEG-400/cluster system could be easily recycled. Spectroscopic studies elucidate a stepwise mechanism: firstly, proton-coupled electron transfer (PCET) involving the transfer of an electron from Cu+ and a proton from imidazole results in the formation of a labile penta-coordinated Cu2+ and aryl radical; the following effective electron transfer from the ferrocene unit reduces Cu2+ and forms the target product; finally, the ferrocenium unit is reduced by the I- anion. The merits of this eco-friendly synthesis are the efficient utilization of reagents and easy recyclability.

Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases

DTIC Science & Technology

2009-05-01

REPORT DATE (DD-MM-YYYY) 31/05/2009 2 . REPORT TYPE Annual 3. DATES COVERED (From - To) 1 MAY 2008-30 APR 2009 4. TITLE AND SUBTITLE Specific...specific” GAG (Objective I) Task 2 : Synthesis of L-, D-, or mixed L/D polyargines (Objective II) Task 3: In vitro and in vivo evaluation of the FITC...tagged polyarginines (Objective II) Months 6 – 24: Task 4: Prepare p-SCN-Bn-CB-TE2A and the multivalent scaffolds (CB-TE2O-(PEG-COOH) 2 or CB- TE2A-(PEG

A teleoperation training simulator with visual and kinesthetic force virtual reality

NASA Technical Reports Server (NTRS)

Kim, Won S.; Schenker, Paul

1992-01-01

A force-reflecting teleoperation training simulator with a high-fidelity real-time graphics display has been developed for operator training. A novel feature of this simulator is that it enables the operator to feel contact forces and torques through a force-reflecting controller during the execution of the simulated peg-in-hole task, providing the operator with the feel of visual and kinesthetic force virtual reality. A peg-in-hole task is used in our simulated teleoperation trainer as a generic teleoperation task. A quasi-static analysis of a two-dimensional peg-in-hole task model has been extended to a three-dimensional model analysis to compute contact forces and torques for a virtual realization of kinesthetic force feedback. The simulator allows the user to specify force reflection gains and stiffness (compliance) values of the manipulator hand for both the three translational and the three rotational axes in Cartesian space. Three viewing modes are provided for graphics display: single view, two split views, and stereoscopic view.

Kinect technology for hand tracking control of surgical robots: technical and surgical skill comparison to current robotic masters.

PubMed

Kim, Yonjae; Leonard, Simon; Shademan, Azad; Krieger, Axel; Kim, Peter C W

2014-06-01

Current surgical robots are controlled by a mechanical master located away from the patient, tracking surgeon's hands by wire and pulleys or mechanical linkage. Contactless hand tracking for surgical robot control is an attractive alternative, because it can be executed with minimal footprint at the patient's bedside without impairing sterility, while eliminating current disassociation between surgeon and patient. We compared technical and technologic feasibility of contactless hand tracking to the current clinical standard master controllers. A hand-tracking system (Kinect™-based 3Gear), a wire-based mechanical master (Mantis Duo), and a clinical mechanical linkage master (da Vinci) were evaluated for technical parameters with strong clinical relevance: system latency, static noise, robot slave tremor, and controller range. Five experienced surgeons performed a skill comparison study, evaluating the three different master controllers for efficiency and accuracy in peg transfer and pointing tasks. da Vinci had the lowest latency of 89 ms, followed by Mantis with 374 ms and 3Gear with 576 ms. Mantis and da Vinci produced zero static error. 3Gear produced average static error of 0.49 mm. The tremor of the robot used by the 3Gear and Mantis system had a radius of 1.7 mm compared with 0.5 mm for da Vinci. The three master controllers all had similar range. The surgeons took 1.98 times longer to complete the peg transfer task with the 3Gear system compared with Mantis, and 2.72 times longer with Mantis compared with da Vinci (p value 2.1e-9). For the pointer task, surgeons were most accurate with da Vinci with average error of 0.72 mm compared with Mantis's 1.61 mm and 3Gear's 2.41 mm (p value 0.00078). Contactless hand-tracking technology as a surgical master can execute simple surgical tasks. Whereas traditional master controllers outperformed, given that contactless hand-tracking is a first-generation technology, clinical potential is promising and could become a reality with some technical improvements.

Hydration induced material transfer in membranes of osmotic pump tablets measured by synchrotron radiation based FTIR.

PubMed

Wu, Li; Yin, Xianzhen; Guo, Zhen; Tong, Yajun; Feng, Jing; York, Peter; Xiao, Tiqiao; Chen, Min; Gu, Jingkai; Zhang, Jiwen

2016-03-10

Osmotic pump tablets are reliable oral controlled drug delivery systems based on their semipermeable membrane coating. This research used synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy and imaging to investigate the hydration induced material transfer in the membranes of osmotic pump tablets. SR-FTIR was applied to record and map the chemical information of a micro-region of the membranes, composed of cellulose acetate (CA, as the water insoluble matrix) and polyethylene glycol (PEG, as the soluble pore forming agent and plasticizing agent). The microstructure and chemical change of membranes hydrated for 0, 5, 10 and 30min were measured using SR-FTIR, combined with scanning electronic microscopy and atom force microscopy. The SR-FTIR microspectroscopy results indicated that there was a major change at the absorption range of 2700-3100cm(-1) in the membranes after different periods of hydration time. The absorption bands at 2870-2880cm(-1) and 2950-2960cm(-1) were assigned to represent CA and PEG, respectively. The chemical group signal distribution illustrated by the ratio of PEG to CA demonstrated that the trigger of drug release in the preliminary stage was due to the rapid transfer of PEG into liquid medium with a sharp decrease of PEG in the membranes. The SR-FTIR mapping results have demonstrated the hydration induced material transfer in the membranes of osmotic pump tablets and enabled reassessment of the drug release mechanism of membrane controlled osmotic pump systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Informed peg-in-hole insertion using optical sensors

NASA Astrophysics Data System (ADS)

Paulos, Eric; Canny, John F.

1993-08-01

Peg-in-hole insertion is not only a longstanding problem in robotics but the most common automated mechanical assembly task. In this paper we present a high precision, self-calibrating peg-in-hole insertion strategy using several very simple, inexpensive, and accurate optical sensors. The self-calibrating feature allows us to achieve successful dead-reckoning insertions with tolerances of 25 microns without any accurate initial position information for the robot, pegs, or holes. The program we implemented works for any cylindrical peg, and the sensing steps do not depend on the peg diameter, which the program does not know. The key to the strategy is the use of a fixed sensor to localize both a mobile sensor and the peg, while the mobile sensor localizes the hole. Our strategy is extremely fast, localizing pegs as they are in route to their insertion location without pausing. The result is that insertion times are dominated by the transport time between pick and place operations.

Synthesis, Characterization, Mechanism of Decomposition, and Antiproliferative Activity of a Class of PEGylated Benzopolysulfanes Structurally Similar to the Natural Product Varacin

PubMed Central

Mahendran, Adaickapillai; Vuong, Angela; Aebisher, David; Gong, Yaqiong; Bittman, Robert; Arthur, Gilbert; Kawamura, Akira; Greer, Alexander

2012-01-01

Benzopolysulfanes, 4-CH3(OCH2CH2)3NHC(O)-C6H4-1,2-Sx (x = 3–7, and 9) were synthesized with a PEG group attached through an amide bond and examined for water solubility, antitumor activity, and propensity to equilibrate and desulfurate. LCMS and HPLC data show the PEG pentasulfane ring structure predominates, and the tri-, tetra-, hexa-, hepta-, and nonasulfanes were present at very low concentrations. The presence of the PEG group improved water solubility by 50-fold compared to the unsubstituted benzopolysulfanes, C6H4Sx (x = 3, 5, and 7), based on intrinsic solubility measurements. Polysulfur linkages in the PEG compounds decomposed in the presence of ethanethiol and hydroxide ion. The PEG pentathiepin desulfurated rapidly and an S3 transfer reaction was observed in the presence of norbornene, no S2 transfer reaction was observed with 2,3-dimethylbutadiene. The antitumor activities of the PEG-substituted benzopolysulfane mixtures were analyzed against four human tumor cell lines PC3 (prostate), DU145 (prostate), MDA-MB-231 (breast), and Jurkat (T-cell leukemia). The PEG conjugated polysulfanes had IC50 values 1.2–5.8 times lower than the parent “unsubstituted” benzopolysulfanes. Complete cell killing was observed for the PEG polysulfanes with 4 μM for PC3 and DU145 cells, and with 12 μM for MDA-MB-231 cells. The results suggest that solubilization of the polysulfur linkage is a key parameter to the success of these compounds as drug leads. PMID:20704430

PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time.

PubMed

Kooijmans, S A A; Fliervoet, L A L; van der Meel, R; Fens, M H A M; Heijnen, H F G; van Bergen En Henegouwen, P M P; Vader, P; Schiffelers, R M

2016-02-28

Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, the therapeutic applicability of EVs may be limited due to a lack of cell-targeting specificity and rapid clearance of exogenous EVs from the circulation. In order to improve EV characteristics for drug delivery to tumor cells, we have developed a novel method for decorating EVs with targeting ligands conjugated to polyethylene glycol (PEG). Nanobodies specific for the epidermal growth factor receptor (EGFR) were conjugated to phospholipid (DMPE)-PEG derivatives to prepare nanobody-PEG-micelles. When micelles were mixed with EVs derived from Neuro2A cells or platelets, a temperature-dependent transfer of nanobody-PEG-lipids to the EV membranes was observed, indicative of a 'post-insertion' mechanism. This process did not affect EV morphology, size distribution, or protein composition. After introduction of PEG-conjugated control nanobodies to EVs, cellular binding was compromised due to the shielding properties of PEG. However, specific binding to EGFR-overexpressing tumor cells was dramatically increased when EGFR-specific nanobodies were employed. Moreover, whereas unmodified EVs were rapidly cleared from the circulation within 10min after intravenous injection in mice, EVs modified with nanobody-PEG-lipids were still detectable in plasma for longer than 60min post-injection. In conclusion, we propose post-insertion as a novel technique to confer targeting capacity to isolated EVs, circumventing the requirement to modify EV-secreting cells. Importantly, insertion of ligand-conjugated PEG-derivatized phospholipids in EV membranes equips EVs with improved cell specificity and prolonged circulation times, potentially increasing EV accumulation in targeted tissues and improving cargo delivery. Copyright © 2015. Published by Elsevier B.V.

Saving robots improves laparoscopic performance: transfer of skills from a serious game to a virtual reality simulator.

PubMed

IJgosse, Wouter M; van Goor, Harry; Luursema, Jan-Maarten

2018-01-18

Residents find it hard to commit to structural laparoscopic skills training. Serious gaming has been proposed as a solution on the premise that it is effective and more motivating than traditional simulation. We establish construct validity for the laparoscopic serious game Underground by comparing laparoscopic simulator performance for a control group and an Underground training group. A four-session laparoscopic basic skills course is part of the medical master students surgical internship at the Radboud University Medical Centre. Four cohorts, representing 107 participants, were assigned to either the Underground group or the control group. The control group trained on the FLS video trainer and the LapSim virtual reality simulator for four sessions. The Underground group played Underground for three sessions followed by a transfer session on the FLS video trainer and the LapSim. To assess the effect of engaging in serious gameplay on performance on two validated laparoscopic simulators, initial performance on the FLS video trainer and the LapSim was compared between the control group (first session) and the Underground group (fourth session). We chose task duration as a proxy for laparoscopic performance. The Underground group outperformed the control group on all three LapSim tasks: Camera navigation F(1) = 12.71, p < .01; Instrument navigation F(1) = 8.04, p < .01; and Coordination F(1) = 6.36, p = .01. There was no significant effect of playing Underground for performance on the FLS video trainer Peg Transfer task, F(1) = 0.28, p = .60. We demonstrated skills transfer between a serious game and validated laparoscopic simulator technology. Serious gaming may become a valuable, cost-effective addition to the skillslab, if transfer to the operating room can be established. Additionally, we discuss sources of transferable skills to help explain our and previous findings.

Synthesis of PEG-rich PLGA-PEG-PLGA for the PLGA-PEG-PLGA/laponite hydrogels with thermoresponsive sol-gel transitions

NASA Astrophysics Data System (ADS)

Tanimoto, Keishi; Maeda, Tomoki; Hotta, Atsushi

Poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) possesses moderate biocompatibility originating from the relatively shorter PEG block in its polymeric molecule. For the maximum utilization of the highly biocompatible PEG block, the PEG block should be relatively longer, and thus the PEG/PLGA ratio, the molecular weight ratio of PEG and PLGA, should be higher. In addition, for the wider use of PLGA-PEG-PLGA in the biological fields, the aqueous PLGA-PEG-PLGA solution should transfer from sol to gel states in response to the increase in temperature. It was reported, however, through the previous researches, that the PLGA-PEG-PLGA solution with a high PEG/PLGA ratio (above 0.5) would not exhibit thermoresponsive sol-gel transitions. In this work, PLGA-PEG-PLGAs with higher PEG/PLGA ratios were synthesized and the laponite, an inorganic nanoparticle, was added to the solutions to realize the thermoresponsive sol-gel transition. It was found that the PLGA-PEG-PLGA with the high PEG/PLGA ratio of 3.0 could exhibit the thermoresponsive sol-gel transition by adding laponite at 1.25 weight percent. The physical characteristics of the gel were also studied by the dynamic mechanical analysis (DMA) This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI\\x9D.

Mastery versus the standard proficiency target for basic laparoscopic skill training: effect on skill transfer and retention.

PubMed

Kolozsvari, Nicoleta O; Kaneva, Pepa; Brace, Chantalle; Chartrand, Genevieve; Vaillancourt, Marilou; Cao, Jiguo; Banaszek, Daniel; Demyttenaere, Sebastian; Vassiliou, Melina C; Fried, Gerald M; Feldman, Liane S

2011-07-01

Little evidence exists to guide educators in the best way to implement simulation within surgical skills curricula. This study investigated whether practicing a basic Fundamentals of Laparoscopic Surgery (FLS) simulator task [peg transfer (PT)] facilitates learning a more complex skill [intracorporeal suturing (ICS)] and compared the effect of PT training to mastery with training to the passing level on PT retention and on learning ICS. For this study, 98 surgically naïve subjects were randomized to one of three PT training groups: control, standard training, and overtraining. All the participants then trained in ICS. The learning curves for ICS were analyzed by estimating the learning plateau and rate using nonlinear regression. Skill retention was assessed by retesting participants 1 month after training. The groups were compared using analysis of variance (ANOVA). Effectiveness of skill transfer was calculated using the transfer effectiveness ratio (TER). Data are presented as mean±standard deviation (p<0.05). The study was completed by 77 participants (28 control, 26 standard, and 23 overtrained subjects). The ICS learning plateau rose with increasing PT training (452±10 vs. 459±10 vs. 467±10; p<0.01). Increased PT training was associated with a trend toward higher initial ICS scores (128±107 vs. 127±110 vs. 183±106; p=0.13) and faster learning rates (15±4 vs. 14±4 vs. 13±4 trials; p=0.10). At retention, there were no differences in PT scores (p=0.5). The PT training took 20±10 min for standard training and 39±20 min for overtraining (p<0.01). Overtrained participants saved 11±5 min in ICS training compared with the control subjects (p=0.04). However, TER was 0.165 for the overtraining group and 0.160 for the standard training group, suggesting that PT overtraining took longer than the time saved on ICS training. For surgically naïve subjects, part-task training with PT alone was associated with slight improvements in the learning curve for ICS. However, overtraining with PT did not improve skill retention, and peg training alone was not an efficient strategy for learning ICS.

Preparation of poly(ethylene glycol) hydrogels with different network structures for the application of enzyme immobilization.

PubMed

Choi, Dongkil; Lee, Woojin; Park, Jinwon; Koh, Wongun

2008-01-01

In this study, poly(ethylene glycol) (PEG)-based hydrogels having different network structures were synthesized by UV-initiated photopolymerization and used for the enzyme immobilization. PEGs with different molecular weight were acrylated by derivatizing both ends with acryloyl chloride and photopolymerization of PEG-diacrylate (PEG-DA) yielded crosslinked hydrogel network within 5 seconds. Attachment of acrylate groups and gelation were confirmed by ATR/FT-IR and FT-Raman spectroscopy. Network structures of hydrogels could be easily controlled by changing the molecular weight (MW) of PEG-DA and characterized by calculating molecular weight between crosslinks and mesh size from the swelling measurement. Synthesis of hydrogels with higher MW of PEG produced less crosslinked hydrogels having higher water content, larger value of Mc and mesh size, which resulted in enhanced mass transfer but loss of mechanical properties. For the enzyme immobilization, glucose oxidase (GOX) was immobilized inside PEG hydrogels by means of physical entrapment and covalent immobilization. Encapsulated GOX were covalently bound to PEG backbone using acryloyl-PEG-N-hydroxysuccinimide and maintained their activity over a week period without leakage. Kinetic study indicated that immobilized enzyme inside hydrogel prepared from higher MW of PEG possessed lower apparent Km (Michaelis-Menten constant) and higher activity.

Catalytic Mechanism of Short Ethoxy Chain Nonylphenol Dehydrogenase Belonging to a Polyethylene Glycol Dehydrogenase Group in the GMC Oxidoreductase Family

PubMed Central

Liu, Xin; Ohta, Takeshi; Kawabata, Takeshi; Kawai, Fusako

2013-01-01

Ethoxy (EO) chain nonylphenol dehydrogenase (NPEO-DH) from Ensifer sp. AS08 and EO chain octylphenol dehydrogenase from Pseudomonas putida share common molecular characteristics with polyethylene glycol (PEG) dehydrogenases (PEG-DH) and comprise a PEG-DH subgroup in the family of glucose-methanol-choline (GMC) oxidoreductases that includes glucose/alcohol oxidase and glucose/choline dehydrogenase. Three-dimensional (3D) molecular modeling suggested that differences in the size, secondary structure and hydropathy in the active site caused differences in their substrate specificities toward EO chain alkylphenols and free PEGs. Based on 3D molecular modeling, site-directed mutagenesis was utilized to introduce mutations into potential catalytic residues of NPEO-DH. From steady state and rapid kinetic characterization of wild type and mutant NPEO-DHs, we can conclude that His465 and Asn507 are directly involved in the catalysis. Asn507 mediates the transfer of proton from a substrate to FAD and His465 transfers the same proton from the reduced flavin to an electron acceptor. PMID:23306149

Catalytic mechanism of short ethoxy chain nonylphenol dehydrogenase belonging to a polyethylene glycol dehydrogenase group in the GMC oxidoreductase family.

PubMed

Liu, Xin; Ohta, Takeshi; Kawabata, Takeshi; Kawai, Fusako

2013-01-10

Ethoxy (EO) chain nonylphenol dehydrogenase (NPEO-DH) from Ensifer sp. AS08 and EO chain octylphenol dehydrogenase from Pseudomonas putida share common molecular characteristics with polyethylene glycol (PEG) dehydrogenases (PEG-DH) and comprise a PEG-DH subgroup in the family of glucose-methanol-choline (GMC) oxidoreductases that includes glucose/alcohol oxidase and glucose/choline dehydrogenase. Three-dimensional (3D) molecular modeling suggested that differences in the size, secondary structure and hydropathy in the active site caused differences in their substrate specificities toward EO chain alkylphenols and free PEGs. Based on 3D molecular modeling, site-directed mutagenesis was utilized to introduce mutations into potential catalytic residues of NPEO-DH. From steady state and rapid kinetic characterization of wild type and mutant NPEO-DHs, we can conclude that His465 and Asn507 are directly involved in the catalysis. Asn507 mediates the transfer of proton from a substrate to FAD and His465 transfers the same proton from the reduced flavin to an electron acceptor.

Electrochemical and XPS study of LiFePO4 cathode nanocomposite with PPy/PEG conductive network

NASA Astrophysics Data System (ADS)

Fedorková, A.; Oriňáková, R.; Oriňák, A.; Kupková, M.; Wiemhöfer, H.-D.; Audinot, J. N.; Guillot, J.

2012-08-01

High performance PPy/PEG-LiFePO4 nanocomposites as cathode materials were synthesized by solvothermal method and simple chemical oxidative polymerization of pyrrole (Py) monomer on the surface of LiFePO4 particles. The samples were characterized by scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectrometry (XPS) and charge-discharge tests. PPyPEG hybrid layers decrease particle to particle contact resistance while the impedance measurements confirmed that the coating of PPy-PEG significantly decreases the charge transfer resistance of the electrode material. The initial discharge capacities of this sample at C/5 and 1C are 150 and 128 mAh/g, respectively. The results show that PPy/PEGLiFePO4 composites are more effective than bare LiFePO4 as cathode material.

Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI).

PubMed

Yu, Tao; Chan, Kannie W Y; Anonuevo, Abraham; Song, Xiaolei; Schuster, Benjamin S; Chattopadhyay, Sumon; Xu, Qingguo; Oskolkov, Nikita; Patel, Himatkumar; Ensign, Laura M; van Zjil, Peter C M; McMahon, Michael T; Hanes, Justin

2015-02-01

Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging ("theranostics"). Here, we describe liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, e.g., the diaCEST MRI contrast agent barbituric acid (BA). We observed that polyethylene glycol (PEG)-coated liposomes containing ≥7 mol% PEG diffused only ~10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol%-PEG liposomes contained sufficient BA loading for diaCEST contrast, and provided improved vaginal distribution compared to 0 and 3mol%-PEG liposomes. However, increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution, suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol%-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces. This team of authors characterized liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, such as barbituric acid (a diaCEST MRI contrast agent) and concluded that liposomal MPP with optimized PEG coating enables drug delivery and imaging at mucosal surfaces. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of a preoperative warm-up with a custom-made Nintendo video game on the performance of laparoscopic surgeons.

PubMed

Jalink, M B; Heineman, E; Pierie, J P E N; ten Cate Hoedemaker, H O

2015-08-01

It has previously been shown that short, pre-operative practice with a simulator, box trainer, or certain video games can temporarily improve one's basic laparoscopic skills; the so-called warm-up effect. In this experiment, we tested the hypothesis that Underground video game made for training basic laparoscopic skills, can also be used for a pre-operative warm-up. 29 laparoscopic experts were randomized into two different groups, which were tested on two different days. Group 1 (n = 16) did a laparoscopic skill baseline measurement using the FLS peg transfer test and the Top Gun cobra rope drill on day 1, and did the same tests on day 2 after a 15 min session with the Underground game. Group 2 (n = 13) did the same, but started with the video game, followed by baseline measurement on day 2. This way, each participant served as its own control. Video recordings of both tasks were later analyzed by two blinded reviewers. On day 1, group 2 was 14.33 % (P = 0.037) faster in completing the peg transfer test. A trend toward better cobra rope scores is also seen. When comparing the average improvement between both days, group 1--which used the game as a warm-up on day 2--showed a 19.61 % improvement in cobra rope score, compared to a 0.77 % score decrease in group 2 (P = 0.002). This study shows that the Underground video game can be used as a pre-operative warm-up in an experimental setting.

Construct and concurrent validity of a Nintendo Wii video game made for training basic laparoscopic skills.

PubMed

Jalink, M B; Goris, J; Heineman, E; Pierie, J P E N; ten Cate Hoedemaker, H O

2014-02-01

Virtual reality (VR) laparoscopic simulators have been around for more than 10 years and have proven to be cost- and time-effective in laparoscopic skills training. However, most simulators are, in our experience, considered less interesting by residents and are often poorly accessible. Consequently, these devices are rarely used in actual training. In an effort to make a low-cost and more attractive simulator, a custom-made Nintendo Wii game was developed. This game could ultimately be used to train the same basic skills as VR laparoscopic simulators ought to. Before such a video game can be implemented into a surgical training program, it has to be validated according to international standards. The main goal of this study was to test construct and concurrent validity of the controls of a prototype of the game. In this study, the basic laparoscopic skills of experts (surgeons, urologists, and gynecologists, n = 15) were compared to those of complete novices (internists, n = 15) using the Wii Laparoscopy (construct validity). Scores were also compared to the Fundamentals of Laparoscopy (FLS) Peg Transfer test, an already established assessment method for measuring basic laparoscopic skills (concurrent validity). Results showed that experts were 111 % faster (P = 0.001) on the Wii Laparoscopy task than novices. Also, scores of the FLS Peg Transfer test and the Wii Laparoscopy showed a significant, high correlation (r = 0.812, P < 0.001). The prototype setup of the Wii Laparoscopy possesses solid construct and concurrent validity.

RAFT Aqueous Dispersion Polymerization Yields Poly(ethylene glycol)-Based Diblock Copolymer Nano-Objects with Predictable Single Phase Morphologies

PubMed Central

2013-01-01

A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by 1H NMR spectroscopy and relatively low diblock copolymer polydispersities (Mw/Mn < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMAx diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG113-PHPMAx phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications. PMID:24400622

Establishment and operation of a biorepository for molecular epidemiologic studies in Costa Rica.

PubMed

Cortés, Bernal; Schiffman, Mark; Herrero, Rolando; Hildesheim, Allan; Jiménez, Silvia; Shea, Katheryn; González, Paula; Porras, Carolina; Fallas, Greivin; Rodríguez, Ana Cecilia

2010-04-01

The Proyecto Epidemiológico Guanacaste (PEG) has conducted several large studies related to human papillomavirus (HPV) and cervical cancer in Guanacaste, Costa Rica in a long-standing collaboration with the U.S. National Cancer Institute. To improve molecular epidemiology efforts and save costs, we have gradually transferred technology to Costa Rica, culminating in state-of-the-art laboratories and a biorepository to support a phase III clinical trial investigating the efficacy of HPV 16/18 vaccine. Here, we describe the rationale and lessons learned in transferring molecular epidemiologic and biorepository technology to a developing country. At the outset of the PEG in the early 1990s, we shipped all specimens to repositories and laboratories in the United States, which created multiple problems. Since then, by intensive personal interactions between experts from the United States and Costa Rica, we have successfully transferred liquid-based cytology, HPV DNA testing and serology, chlamydia and gonorrhea testing, PCR-safe tissue processing, and viable cryopreservation. To accommodate the vaccine trial, a state-of-the-art repository opened in mid-2004. Approximately 15,000 to 50,000 samples are housed in the repository on any given day, and >500,000 specimens have been shipped, many using a custom-made dry shipper that permits exporting >20,000 specimens at a time. Quality control of shipments received by the NCI biorepository has revealed an error rate of <0.2%. Recently, the PEG repository has incorporated other activities; for example, large-scale aliquotting and long-term, cost-efficient storage of frozen specimens returned from the United States. Using Internet-based specimen tracking software has proven to be efficient even across borders. For long-standing collaborations, it makes sense to transfer the molecular epidemiology expertise toward the source of specimens. The successes of the PEG molecular epidemiology laboratories and biorepository prove that the physical and informatics infrastructures of a modern biorepository can be transferred to a resource-limited and weather-challenged region. Technology transfer is an important and feasible goal of international collaborations.

Development of stereo endoscope system with its innovative master interface for continuous surgical operation.

PubMed

Kim, Myungjoon; Lee, Chiwon; Hong, Nhayoung; Kim, Yoon Jae; Kim, Sungwan

2017-06-24

Although robotic laparoscopic surgery has various benefits when compared with conventional open surgery and minimally invasive surgery, it also has issues to overcome and one of the issues is the discontinuous surgical flow that occurs whenever control is swapped between the endoscope system and the operating robot arm system. This can lead to problems such as collision between surgical instruments, injury to patients, and increased operation time. To achieve continuous surgical operation, a wireless controllable stereo endoscope system is proposed which enables the simultaneous control of the operating robot arm system and the endoscope system. The proposed system consists of two improved novel master interfaces (iNMIs), a four-degrees of freedom (4-DOFs) endoscope control system (ECS), and a simple three-dimensional (3D) endoscope. In order to simultaneously control the proposed system and patient side manipulators of da Vinci research kit (dVRK), the iNMIs are installed to the master tool manipulators of dVRK system. The 4-DOFs ECS consists of four servo motors and employs a two-parallel link structure to provide translational and fulcrum point motion to the simple 3D endoscope. The images acquired by the endoscope undergo stereo calibration and rectification to provide a clear 3D vision to the surgeon as available in clinically used da Vinci surgical robot systems. Tests designed to verify the accuracy, data transfer time, and power consumption of the iNMIs were performed. The workspace was calculated to estimate clinical applicability and a modified peg transfer task was conducted with three novice volunteers. The iNMIs operated for 317 min and moved in accordance with the surgeon's desire with a mean latency of 5 ms. The workspace was calculated to be 20378.3 cm 3 , which exceeds the reference workspace of 549.5 cm 3 . The novice volunteers were able to successfully execute the modified peg transfer task designed to evaluate the proposed system's overall performance. The experimental results verify that the proposed 3D endoscope system enables continuous surgical flow. The workspace is suitable for the performance of numerous types of surgeries. Therefore, the proposed system is expected to provide much higher safety and efficacy for current surgical robot systems.

The impact of visual scanning in the laparoscopic environment after engaging in strain coping.

PubMed

Klein, Martina I; DeLucia, Patricia R; Olmstead, Ryan

2013-06-01

We aimed to determine whether visual scanning has a detrimental impact on the monitoring of critical signals and the performance of a concurrent laparoscopic training task after participants engaged in Hockey's strain coping. Strain coping refers to straining cognitive (attentional) resources joined with latent decrements (i.e., stress). DeLucia and Betts (2008) reported that monitoring critical signals degraded performance of a laparoscopic peg-reversal task compared with no monitoring. However, performance did not differ between displays in which critical signals were shown on split screens (less visual scanning) and separated displays (more visual scanning). We hypothesized that effects of scanning may occur after prolonged strain coping. Using a between-subjects design, we had undergraduates perform a laparoscopic training task that induced strain coping. Then they performed a laparoscopic peg-reversal task while monitoring critical signals with a split-screen or separated display. We administered the NASA-Task Load Index (TLX) and Dundee Stress State Questionnaire (DSSQ) to assess strain coping. The TLX and DSSQ profiles indicated that participants engaged in strain coping. Monitoring critical signals resulted in slowed peg-reversal performance compared with no monitoring. Separated displays degraded critical-signal monitoring compared with split-screen displays. After novice observers experience strain coping, visual scanning can impair the detection of critical signals. Results suggest that the design and arrangement of displays in the operating room must incorporate the attentional limitations of the surgeon. Designs that induce visual scanning may impair monitoring of critical information at least in novices. Presenting displays closely in space may be beneficial.

Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

PubMed

Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

2014-05-05

Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

Aerobic TCE degradation by encapsulated toluene-oxidizing bacteria, Pseudomonas putida and Bacillus spp.

PubMed

Kim, Seungjin; Bae, Wookeun; Hwang, Jungmin; Park, Jaewoo

2010-01-01

The degradation rates of toluene and trichloroethylene (TCE) by Pseudomonas putida and Bacillus spp. that were encapsulated in polyethylene glycol (PEG) polymers were evaluated in comparison with the results of exposure to suspended cultures. PEG monomers were polymerized together with TCE-degrading microorganisms, such that the cells were encapsulated in and protected by the matrices of the PEG polymers. TCE concentrations were varied from 0.1 to 1.5 mg/L. In the suspended cultures of P. putida, the TCE removal rate decreased as the initial TCE concentration increased, revealing TCE toxicity or a limitation of reducing power, or both. When the cells were encapsulated, an initial lag period of about 10-20 h was observed for toluene degradation. Once acclimated, the encapsulated P. putida cultures were more tolerant to TCE at an experimental range of 0.6-1.0 mg/L and gave higher transfer efficiencies (mass TCE transformed/mass toluene utilized). When the TCE concentration was low (e.g., 0.1 mg/L) the removal of TCE per unit mass of cells (specific removal) was significantly lower, probably due to a diffusion limitation into the PEG pellet. Encapsulated Bacillus spp. were able to degrade TCE cometabolically. The encapsulated Bacillus spp. gave significantly higher values than did P. putida in the specific removal and the transfer efficiency, particularly at relatively high TCE concentration of approximately 1.0±0.5 mg/L. The transfer efficiency by encapsulated Bacillus spp. in this study was 0.27 mgTCE/mgToluene, which was one to two orders of magnitude greater than the reported values.

Fabrication of Polymeric Micelles with Aggregation-Induced Emission and Forster Resonance Energy Transfer for Anticancer Drug Delivery.

PubMed

Hao, Na; Sun, Changzhen; Wu, Zhengfei; Xu, Long; Gao, Wenxia; Cao, Jun; Li, Li; He, Bin

2017-07-19

With the aim of obtaining effective cancer therapy with simultaneous cellular imaging, dynamic drug-release monitoring, and chemotherapeutic treatment, a polymeric micelle with aggregation-induced emission (AIE) imaging and a Forster resonance energy transfer (FRET) effect was fabricated as the drug carrier. An amphiphilic conjugate of 1H-pyrrole-1-propanoicacid (MAL)-poly(ethylene glycol) (PEG)-Tripp-bearing AIE molecules were synthesized and self-assembled into micelles to load the anticancer drug doxorubicin (DOX). Spherical DOX-loaded micelles with the mean size of 106 nm were obtained with good physiological stability (CMC, 12.5 μg/mL), high drug-loading capacity (10.4%), and encapsulation efficiency (86%). The cellular uptake behavior of DOX-loaded MAL-PEG-Tripp micelles was visible for high-quality intracellular imaging due to the AIE property. The delivery of DOX from the drug-loaded micelles was dynamic monitored by the FRET effect between the DOX and MAL-PEG-Tripp. Both in vitro (IC50, 2.36 μg/mL) and in vivo anticancer activity tests revealed that the DOX-loaded MAL-PEG-Tripp micelles exhibited promising therapeutic efficacy to cancer with low systematic toxicity. In summary, this micelle provided an effective way to fabricate novel nanoplatform for intracellular imaging, drug-delivery tracing, and chemotherapy.

Time-resolved IUE studies of cataclysmic variables. I - Eclipsing systems IP Peg, PG 1030+590, and V1315 Aql

NASA Technical Reports Server (NTRS)

Szkody, Paula

1987-01-01

IUE time-resolved spectra of the high-inclination cataclysmic variables IP Peg, PG 1030+590, and V1315 Aql are analyzed in order to determine the characteristics of the disk, hotspots, and white dwarfs. The UV continuum flux distributions are generally flatter than systems of low inclination and high mass-transfer rate, and the white dwarfs/inner disk appear to be relatively cool (15,000-19,000 K) for their orbital periods, possibly because the boundary layers are blocked from view. The continuum fluxes increase at spot phases, with the spot providing the dominant flux in IP Peg. The spot temperatures range from hot (20,000 K) in IP Peg, and perhaps in PG 1030+590, to cool (11,000 K) in V1315 Aql. The C IV emission lines show slightly larger decreases at spot phases than during eclipse, which implies an extended stream area.

Changing the Learning Curve in Novice Laparoscopists: Incorporating Direct Visualization into the Simulation Training Program.

PubMed

Dawidek, Mark T; Roach, Victoria A; Ott, Michael C; Wilson, Timothy D

A major challenge in laparoscopic surgery is the lack of depth perception. With the development and continued improvement of 3D video technology, the potential benefit of restoring 3D vision to laparoscopy has received substantial attention from the surgical community. Despite this, procedures conducted under 2D vision remain the standard of care, and trainees must become proficient in 2D laparoscopy. This study aims to determine whether incorporating 3D vision into a 2D laparoscopic simulation curriculum accelerates skill acquisition in novices. Postgraduate year-1 surgical specialty residents (n = 15) at the Schulich School of Medicine and Dentistry, at Western University were randomized into 1 of 2 groups. The control group practiced the Fundamentals of Laparoscopic Surgery peg-transfer task to proficiency exclusively under standard 2D laparoscopy conditions. The experimental group first practiced peg transfer under 3D direct visualization, with direct visualization of the working field. Upon reaching proficiency, this group underwent a perceptual switch, changing to standard 2D laparoscopy conditions, and once again trained to proficiency. Incorporating 3D direct visualization before training under standard 2D conditions significantly (p < 0.0.5) reduced the total training time to proficiency by 10.9 minutes or 32.4%. There was no difference in total number of repetitions to proficiency. Data were also used to generate learning curves for each respective training protocol. An adaptive learning approach, which incorporates 3D direct visualization into a 2D laparoscopic simulation curriculum, accelerates skill acquisition. This is in contrast to previous work, possibly owing to the proficiency-based methodology employed, and has implications for resource savings in surgical training. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Langmuir and Langmuir-Blodgett films of multifunctional, amphiphilic polyethers with cholesterol moieties.

PubMed

Reuter, Sascha; Hofmann, Anna M; Busse, Karsten; Frey, Holger; Kressler, Jörg

2011-03-01

Langmuir films of multifunctional, hydrophilic polyethers containing a hydrophobic cholesterol group (Ch) were studied by surface pressure-mean molecular area (π-mmA) measurements and Brewster angle microscopy (BAM). The polyethers were either homopolymers or diblock copolymers of linear poly(glycerol) (lPG), linear poly(glyceryl glycidyl ether) (lPGG), linear poly(ethylene glycol) (lPEG), or hyperbranched poly(glycerol) (hbPG). Surface pressure measurements revealed that the homopolymers lPG and hbPG did not stay at the water surface after spreading and solvent evaporation, in contrast to lPEG. Because of the incorporation of the Ch group in the polymer structure, stable Langmuir films were formed by Ch-lPG(n), Ch-lPGG(n), and Ch-hbPG(n). The Ch-hbPG(n), Ch-lPEG(n), Ch-lPEG(n)-b-lPG(m), Ch-lPEG(n)-b-lPGG(m), and Ch-lPEG(n)-b-hbPG(m) systems showed an extended plateau region assigned to a phase transition involving the Ch groups. Typical hierarchically ordered morphologies of the LB films on hydrophilic substrates were observed for all Ch-initiated polymers. All LB films showed that Ch of the Ch-initiated homopolymers is able to crystallize. This strong tendency of self-aggregation then triggers further dewetting effects of the respective polyether entities. Fingerlike morphologies are observed for Ch-lPEG(69), since the lPEG(69) entity is able to undergo crystallization after transfer onto the silicon substrate.

Comparison of different sets of instruments for laparoendoscopic single-site surgery in a surgical simulator with novices.

PubMed

Wang, Dong; Shi, Long-Qing; Wang, Jing-Min; Jiang, Xiao-Hua; Ji, Zhen-Ling

2016-04-01

Given the parallel entry of working instruments through a single incision in laparoendoscopic single-site surgery, loss of triangulation in the abdominal cavity and counteracting movements of the instruments are inevitable obstacles. Some specially designed devices have emerged to ameliorate these challenges. Twenty-four novice participants were randomized into four groups using assigned instruments, conventional straight instruments, single-curved instruments, double-curved instruments and articulating instruments, respectively, to perform two basic tasks (peg transferring and pattern cutting) 14 times in a modified simulator. A test of the tasks and a resection of the intestine segment of a rat were performed. The task scores and evaluation of intraoperative skills during the resection of the intestine segment were recorded. The instrument of modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) was completed. The task scores of the groups using single-curved instruments and articulating instruments were better than the other two groups on the simulator tasks, consistent with the evaluation of intraoperative skills during the resection of intestine segment. As the proficiency with the instruments increased, the task scores improved, as demonstrated by the learning curve. The workload measured by the modified NASA-TLX tool demonstrated that the groups using articulating instruments and double-curved instruments had a heavier workload in most of the categories compared with the other two groups. Single-curved and articulating instruments are more effective than conventional straight and double-curved devices, and are favourable in laparoendoscopic single-site surgery for novice learners. © 2013 Royal Australasian College of Surgeons.

Usefulness of virtual reality in assessment of medical student laparoscopic skill.

PubMed

Matzke, Josh; Ziegler, Craig; Martin, Kevin; Crawford, Stuart; Sutton, Erica

2017-05-01

This study evaluates if undergraduate medical trainees' laparoscopic skills acquisition could be assessed using a virtual reality (VR) simulator and how the resultant metrics correlate with performance of Fundamentals of Laparoscopic Surgery (FLS) tasks. Our hypothesis is that the VR simulator metrics will correlate with passing results in a competency-based curriculum (FLS). Twenty-eight fourth-year medical students applying for surgical residency were recruited to participate in a VR training curriculum comprised of camera navigation, hand eye coordination, and FLS tasks: circle cutting (CC), ligating loop (LL), peg transfer (PT), and intracorporeal knot tying (IKT). Students were given 8 wk to achieve proficiency goals, after which they were observed performing FLS tasks. The ability of the VR simulator to detect penalties in each of the FLS tasks and correlations of time taken to complete tasks are reported. Twenty-five students trained in all components of the curriculum. All students were proficient in camera navigation and hand eye coordination tasks. Proficiency was achieved in CC, LL, PT, and IKT by 21, 19, 23, and one student, respectively. VR simulation showed high specificity for predicting zero penalties on the observed CC, LL, and PT tasks (80%, 75%, and 80%, respectively). VR can be used to assess medical student's acquisition of laparoscopic skills. The absence of penalties in the simulator reasonably predicts the absence of penalties in all FLS skills, except IKT. The skills acquired by trainees can be used in residency for further monitoring of progress toward proficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of cellular uptake and gene transfer efficiency of pegylated poly-L-lysine compacted DNA: implications for cancer gene therapy.

PubMed

Walsh, M; Tangney, M; O'Neill, M J; Larkin, J O; Soden, D M; McKenna, S L; Darcy, R; O'Sullivan, G C; O'Driscoll, C M

2006-01-01

Recent success in phase I/II clinical trials (Konstan, M. W.; Davis, P. B.; Wagener, J. S.; Hilliard, K. A.; Stern, R. C.; Milgram, L. J.; Kowalczyk, T. H.; Hyatt, S. L.; Fink, T. L.; Gedeon, C. R.; Oette, S. M.; Payne, J. M.; Muhammad, O.; Ziady, A. G.; Moen, R. C.; Cooper, M. J. Hum. Gene Ther. 2004, 15 (12), 1255-69) has highlighted pegylated poly-L-lysine (C1K30-PEG) as a nonviral gene delivery agent capable of achieving clinically significant gene transfer levels in vivo. This study investigates the potential of a C1K30-PEG gene delivery system for cancer gene therapy and evaluates its mode of cellular entry with the purpose of developing an optimally formulated prototype for tumor cell transfection. C1K30-PEG complexes have a neutral charge and form rod-like and toroid-like nanoparticles. Comparison of the transfection efficiency achieved by C1K30-PEG with other cationic lipid and polymeric vectors demonstrates that C1K30-PEG transfects cells more efficiently than unpegylated poly-L-lysine and compares well to commercially available vectors. In vivo gene delivery by C1K30-PEG nanoparticles to a growing subcutaneous murine tumor was also demonstrated. To determine potential barriers to C1K30-PEG gene delivery, the entry mechanism and intracellular fate of rhodamine labeled complexes were investigated. Using cellular markers to delineate the pathway taken by the complexes upon cellular entry, only minor colocalization was observed with EEA-1, a marker of early endosomes. No colocalization was observed between the complexes and the transferrin receptor, which is a marker for clathrin-coated pits. In addition, complexes were not observed to enter late endosomes/lysosomes. Cellular entry of the complexes was completely inhibited by the macropinocytosis inhibitor, amiloride, indicating that the complexes enter cells via macropinosomes. Such mechanistic studies are an essential step to support future rational design of pegylated poly-L-lysine vectors to improve the efficiency of gene delivery.

Antitumor effect of nuclear factor-κB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites

PubMed Central

Kono, Yusuke; Kawakami, Shigeru; Higuchi, Yuriko; Maruyama, Kazuo; Yamashita, Fumiyoshi; Hashida, Mitsuru

2014-01-01

Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear factor-κB (NF-κB) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a NF-κB decoy into TAMs by ultrasound (US)-responsive, mannose-modified liposome/NF-κB decoy complexes (Man-PEG bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of NF-κB decoy transfection into TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure transferred the NF-κB decoy into TAMs effectively. When the NF-κB decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL-12, tumor necrosis factor-α, and IL-6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF-κB decoy transfer into TAMs significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a NF-κB decoy efficiently by Man-PEG bubble lipoplexes with US exposure into TAMs, which may be a novel approach for MA treatment. PMID:24850474

Emergent selectivity for task-relevant stimuli in higher-order auditory cortex

PubMed Central

Atiani, Serin; David, Stephen V.; Elgueda, Diego; Locastro, Michael; Radtke-Schuller, Susanne; Shamma, Shihab A.; Fritz, Jonathan B.

2014-01-01

A variety of attention-related effects have been demonstrated in primary auditory cortex (A1). However, an understanding of the functional role of higher auditory cortical areas in guiding attention to acoustic stimuli has been elusive. We recorded from neurons in two tonotopic cortical belt areas in the dorsal posterior ectosylvian gyrus (dPEG) of ferrets trained on a simple auditory discrimination task. Neurons in dPEG showed similar basic auditory tuning properties to A1, but during behavior we observed marked differences between these areas. In the belt areas, changes in neuronal firing rate and response dynamics greatly enhanced responses to target stimuli relative to distractors, allowing for greater attentional selection during active listening. Consistent with existing anatomical evidence, the pattern of sensory tuning and behavioral modulation in auditory belt cortex links the spectro-temporal representation of the whole acoustic scene in A1 to a more abstracted representation of task-relevant stimuli observed in frontal cortex. PMID:24742467

Comparison of precision and speed in laparoscopic and robot-assisted surgical task performance.

PubMed

Zihni, Ahmed; Gerull, William D; Cavallo, Jaime A; Ge, Tianjia; Ray, Shuddhadeb; Chiu, Jason; Brunt, L Michael; Awad, Michael M

2018-03-01

Robotic platforms have the potential advantage of providing additional dexterity and precision to surgeons while performing complex laparoscopic tasks, especially for those in training. Few quantitative evaluations of surgical task performance comparing laparoscopic and robotic platforms among surgeons of varying experience levels have been done. We compared measures of quality and efficiency of Fundamentals of Laparoscopic Surgery task performance on these platforms in novices and experienced laparoscopic and robotic surgeons. Fourteen novices, 12 expert laparoscopic surgeons (>100 laparoscopic procedures performed, no robotics experience), and five expert robotic surgeons (>25 robotic procedures performed) performed three Fundamentals of Laparoscopic Surgery tasks on both laparoscopic and robotic platforms: peg transfer (PT), pattern cutting (PC), and intracorporeal suturing. All tasks were repeated three times by each subject on each platform in a randomized order. Mean completion times and mean errors per trial (EPT) were calculated for each task on both platforms. Results were compared using Student's t-test (P < 0.05 considered statistically significant). Among novices, greater errors were noted during laparoscopic PC (Lap 2.21 versus Robot 0.88 EPT, P < 0.001). Among expert laparoscopists, greater errors were noted during laparoscopic PT compared with robotic (PT: Lap 0.14 versus Robot 0.00 EPT, P = 0.04). Among expert robotic surgeons, greater errors were noted during laparoscopic PC compared with robotic (Lap 0.80 versus Robot 0.13 EPT, P = 0.02). Among expert laparoscopists, task performance was slower on the robotic platform compared with laparoscopy. In comparisons of expert laparoscopists performing tasks on the laparoscopic platform and expert robotic surgeons performing tasks on the robotic platform, expert robotic surgeons demonstrated fewer errors during the PC task (P = 0.009). Robotic assistance provided a reduction in errors at all experience levels for some laparoscopic tasks, but no benefit in the speed of task performance. Robotic assistance may provide some benefit in precision of surgical task performance. Copyright © 2017 Elsevier Inc. All rights reserved.

PEGylated carbon nanotubes impair retrieval of contextual fear memory and alter oxidative stress parameters in the rat hippocampus.

PubMed

Dal Bosco, Lidiane; Weber, Gisele E B; Parfitt, Gustavo M; Paese, Karina; Gonçalves, Carla O F; Serodre, Tiago M; Furtado, Clascídia A; Santos, Adelina P; Monserrat, José M; Barros, Daniela M

2015-01-01

Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions.

PEGylated Carbon Nanotubes Impair Retrieval of Contextual Fear Memory and Alter Oxidative Stress Parameters in the Rat Hippocampus

PubMed Central

Dal Bosco, Lidiane; Weber, Gisele E. B.; Parfitt, Gustavo M.; Paese, Karina; Gonçalves, Carla O. F.; Serodre, Tiago M.; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

2015-01-01

Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions. PMID:25738149

Enhanced cell uptake via non-covalent decollation of a single-walled carbon nanotube-DNA hybrid with polyethylene glycol-grafted poly(l-lysine) labeled with an Alexa-dye and its efficient uptake in a cancer cell

NASA Astrophysics Data System (ADS)

Fujigaya, Tsuyohiko; Yamamoto, Yuki; Kano, Arihiro; Maruyama, Atsushi; Nakashima, Naotoshi

2011-10-01

The use of single-walled carbon nanotubes (SWNTs) for biomedical applications is a promising approach due to their unique outer optical stimuli response properties, such as a photothermal response triggered by near-IR laser irradiation. The challenging task in order to realize such applications is to render the SWNTs biocompatible. For this purpose, the stable and homogeneous functionalization of the SWNTs with a molecule carrying a biocompatible group is very important. Here, we describe the design and synthesis of a polyanionic SWNT/DNA hybrid combined with a cationic poly(l-lysine) grafted by polyethylene glycol (PLL-g-PEG) to provide a supramolecular SWNT assembly. A titration experiment revealed that the assembly undergoes an approximately 1 : 1 reaction of the SWNT/DNA with PLL-g-PEG. We also found that SWNT/DNA is coated with PLL-g-PEG very homogeneously that avoids the non-specific binding of proteins on the SWNT surface. The experiment using the obtained supramolecular hybrid was carried out in vitro and a dramatic enhancement in the cell uptake efficiency compared to that of the SWNT/DNA hybrid without PLL-g-PEG was found.The use of single-walled carbon nanotubes (SWNTs) for biomedical applications is a promising approach due to their unique outer optical stimuli response properties, such as a photothermal response triggered by near-IR laser irradiation. The challenging task in order to realize such applications is to render the SWNTs biocompatible. For this purpose, the stable and homogeneous functionalization of the SWNTs with a molecule carrying a biocompatible group is very important. Here, we describe the design and synthesis of a polyanionic SWNT/DNA hybrid combined with a cationic poly(l-lysine) grafted by polyethylene glycol (PLL-g-PEG) to provide a supramolecular SWNT assembly. A titration experiment revealed that the assembly undergoes an approximately 1 : 1 reaction of the SWNT/DNA with PLL-g-PEG. We also found that SWNT/DNA is coated with PLL-g-PEG very homogeneously that avoids the non-specific binding of proteins on the SWNT surface. The experiment using the obtained supramolecular hybrid was carried out in vitro and a dramatic enhancement in the cell uptake efficiency compared to that of the SWNT/DNA hybrid without PLL-g-PEG was found. Electronic supplementary information (ESI) available: Additional absorption spectra, DLS plots and PL spectra. See DOI: 10.1039/c1nr10635j

Direct peptide bioconjugation/PEGylation at tyrosine with linear and branched polymeric diazonium salts.

PubMed

Jones, Mathew W; Mantovani, Giuseppe; Blindauer, Claudia A; Ryan, Sinead M; Wang, Xuexuan; Brayden, David J; Haddleton, David M

2012-05-02

Direct polymer conjugation at peptide tyrosine residues is described. In this study Tyr residues of both leucine enkephalin and salmon calcitonin (sCT) were targeted using appropriate diazonium salt-terminated linear monomethoxy poly(ethylene glycol)s (mPEGs) and poly(mPEG) methacrylate prepared by atom transfer radical polymerization. Judicious choice of the reaction conditions-pH, stoichiometry, and chemical structure of diazonium salt-led to a high degree of site-specificity in the conjugation reaction, even in the presence of competitive peptide amino acid targets such as histidine, lysines, and N-terminal amine. In vitro studies showed that conjugation of mPEG(2000) to sCT did not affect the peptide's ability to increase intracellular cAMP induced in T47D human breast cancer cells bearing sCT receptors. Preliminary in vivo investigation showed preserved ability to reduce [Ca(2+)] plasma levels by mPEG(2000)-sCT conjugate in rat animal models. © 2012 American Chemical Society

Muscle oxygenation and glycolysis in females with trapezius myalgia during stress and repetitive work using microdialysis and NIRS.

PubMed

Sjøgaard, Gisela; Rosendal, Lars; Kristiansen, Jesper; Blangsted, Anne K; Skotte, Jørgen; Larsson, Britt; Gerdle, Björn; Saltin, Bengt; Søgaard, Karen

2010-03-01

The aim of this investigation was to study female workers active in the labour market for differences between those with trapezius myalgia (MYA) and without (CON) during repetitive pegboard (PEG) and stress (STR) tasks regarding (1) relative muscle load, (2) trapezius muscle blood flow, (3) metabolite accumulation, (4) oxygenation, and (5) pain development. Among 812 female employees (age 30-60 years) at 7 companies with high prevalence of neck/shoulder complaints, clinical examination identified 43 MYA and 19 CON. At rest, during PEG, and STR the trapezius muscle was measured using (1) EMG and MMG, (2) microdialysis, and (3) NIRS. Further, subjective pain ratings were scored (VAS). EMGrms in %MVE (Maximal Voluntary EMG-activity), was significantly higher among MYA than CON during PEG (11.74 +/- 9.09 vs. 7.42 +/- 5.56%MVE) and STR (5.47 +/- 5.00 vs. 3.28 +/- 1.94%MVE). MANOVA showed a group and time effect regarding data from the microdialysis: for MYA versus CON group differences demonstrated lower muscle blood flow and higher lactate and pyruvate concentrations. Potassium and glucose only showed time effects. NIRS showed similar initial decreases in oxygenation with PEG in both groups, but only in CON a significant increase back to baseline during PEG. VAS score at rest was highest among MYA and increased during PEG, but not for CON. The results showed significant differences between CON and MYA regarding muscle metabolism at rest and with PEG and STR. Higher relative muscle load during PEG and STR, insufficient muscle blood flow and oxygenation may account for the higher lactate, pyruvate and pain responses among MYA versus CON.

Exercising Spatiotemporal Control of Cell Attachment with Optically Transparent Microelectrodes

PubMed Central

Shah, Sunny S.; Lee, Ji Youn; Verkhoturov, Stanislav; Tuleuova, Nazgul; Schweikert, Emile A.; Ramanculov, Erlan; Revzin, Alexander

2013-01-01

This paper describes a novel approach of controlling cell-surface interactions through an electrochemical “switching” of biointerfacial properties of optically transparent microelectrodes. The indium tin oxide (ITO) microelectrodes, fabricated on glass substrates, were modified with poly(ethylene glycol) (PEG) silane to make glass and ITO regions resistant to protein and cell adhesion. Cyclic voltammetry, with potassium ferricyanide serving as a redox reporter molecule, was used to monitor electron transfer across the electrolyte–ITO interface. PEG silane modification of ITO correlated with diminished electron transfer, judged by the disappearance of ferricyanide redox activity. Importantly, application of reductive potential (−1.4 V vs Ag/AgCl reference) corresponded with reappearance of typical ferricyanide redox peaks, thus pointing to desorption of an insulating PEG silane layer. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) characterization of the silanized ITO surfaces after electrical stimulation indicated complete removal of the silane layer. Significantly, electrical stimulation allowed to “switch” chosen electrodes from nonfouling to protein-adhesive while leaving other ITO and glass regions protected by a nonfouling PEG silane layer. The spatial and temporal control of biointerfacial properties afforded by our approach was utilized to micropattern proteins and cells and to construct micropatterned co-cultures. In the future, control of the biointerfacial properties afforded by this novel approach may allow the organization of multiple cell types into precise geometric configurations in order to create better in vitro mimics of cellular complexity of the native tissues. PMID:18512875

FLS tasks can be used as an ergonomic discriminator between laparoscopic and robotic surgery.

PubMed

Zihni, Ahmed M; Ohu, Ikechukwu; Cavallo, Jaime A; Ousley, Jenny; Cho, Sohyung; Awad, Michael M

2014-08-01

Robotic surgery may result in ergonomic benefits to surgeons. In this pilot study, we utilize surface electromyography (sEMG) to describe a method for identifying ergonomic differences between laparoscopic and robotic platforms using validated Fundamentals of Laparoscopic Surgery (FLS) tasks. We hypothesize that FLS task performance on laparoscopic and robotic surgical platforms will produce significant differences in mean muscle activation, as quantified by sEMG. Six right-hand-dominant subjects with varying experience performed FLS peg transfer (PT), pattern cutting (PC), and intracorporeal suturing (IS) tasks on laparoscopic and robotic platforms. sEMG measurements were obtained from each subject's bilateral bicep, tricep, deltoid, and trapezius muscles. EMG measurements were normalized to the maximum voluntary contraction (MVC) of each muscle of each subject. Subjects repeated each task three times per platform, and mean values used for pooled analysis. Average normalized muscle activation (%MVC) was calculated for each muscle group in all subjects for each FLS task. We compared mean %MVC values with paired t tests and considered differences with a p value less than 0.05 to be statistically significant. Mean activation of right bicep (2.7 %MVC lap, 1.3 %MVC robotic, p = 0.019) and right deltoid muscles (2.4 %MVC lap, 1.0 %MVC robotic, p = 0.019) were significantly elevated during the laparoscopic compared to the robotic IS task. The mean activation of the right trapezius muscle was significantly elevated during robotic compared to the laparoscopic PT (1.6 %MVC lap, 3.5 %MVC robotic, p = 0.040) and PC (1.3 %MVC lap, 3.6 %MVC robotic, p = 0.0018) tasks. FLS tasks are validated, readily available instruments that are feasible for use in demonstrating ergonomic differences between surgical platforms. In this study, we used FLS tasks to compare mean muscle activation of four muscle groups during laparoscopic and robotic task performance. FLS tasks can serve as the basis for larger studies to further describe ergonomic differences between laparoscopic and robotic surgery.

Modeling the convergence accommodation of stereo vision for binocular endoscopy.

PubMed

Gao, Yuanqian; Li, Jinhua; Li, Jianmin; Wang, Shuxin

2018-02-01

The stereo laparoscope is an important tool for achieving depth perception in robot-assisted minimally invasive surgery (MIS). A dynamic convergence accommodation algorithm is proposed to improve the viewing experience and achieve accurate depth perception. Based on the principle of the human vision system, a positional kinematic model of the binocular view system is established. The imaging plane pair is rectified to ensure that the two rectified virtual optical axes intersect at the fixation target to provide immersive depth perception. Stereo disparity was simulated with the roll and pitch movements of the binocular system. The chessboard test and the endoscopic peg transfer task were performed, and the results demonstrated the improved disparity distribution and robustness of the proposed convergence accommodation method with respect to the position of the fixation target. This method offers a new solution for effective depth perception with the stereo laparoscopes used in robot-assisted MIS. Copyright © 2017 John Wiley & Sons, Ltd.

The effect of divided attention on novices and experts in laparoscopic task performance.

PubMed

Ghazanfar, Mudassar Ali; Cook, Malcolm; Tang, Benjie; Tait, Iain; Alijani, Afshin

2015-03-01

Attention is important for the skilful execution of surgery. The surgeon's attention during surgery is divided between surgery and outside distractions. The effect of this divided attention has not been well studied previously. We aimed to compare the effect of dividing attention of novices and experts on a laparoscopic task performance. Following ethical approval, 25 novices and 9 expert surgeons performed a standardised peg transfer task in a laboratory setup under three randomly assigned conditions: silent as control condition and two standardised auditory distracting tasks requiring response (easy and difficult) as study conditions. Human reliability assessment was used for surgical task analysis. Primary outcome measures were correct auditory responses, task time, number of surgical errors and instrument movements. Secondary outcome measures included error rate, error probability and hand specific differences. Non-parametric statistics were used for data analysis. 21109 movements and 9036 total errors were analysed. Novices had increased mean task completion time (seconds) (171 ± 44SD vs. 149 ± 34, p < 0.05), number of total movements (227 ± 27 vs. 213 ± 26, p < 0.05) and number of errors (127 ± 51 vs. 96 ± 28, p < 0.05) during difficult study conditions compared to control. The correct responses to auditory stimuli were less frequent in experts (68 %) compared to novices (80 %). There was a positive correlation between error rate and error probability in novices (r (2) = 0.533, p < 0.05) but not in experts (r (2) = 0.346, p > 0.05). Divided attention conditions in theatre environment require careful consideration during surgical training as the junior surgeons are less able to focus their attention during these conditions.

Retention of laparoscopic and robotic skills among medical students: a randomized controlled trial.

PubMed

Orlando, Megan S; Thomaier, Lauren; Abernethy, Melinda G; Chen, Chi Chiung Grace

2017-08-01

Although simulation training beneficially contributes to traditional surgical training, there are less objective data on simulation skills retention. To investigate the retention of laparoscopic and robotic skills after simulation training. We present the second stage of a randomized single-blinded controlled trial in which 40 simulation-naïve medical students were randomly assigned to practice peg transfer tasks on either laparoscopic (N = 20, Fundamentals of Laparoscopic Surgery, Venture Technologies Inc., Waltham, MA) or robotic (N = 20, dV-Trainer, Mimic, Seattle, WA) platforms. In the first stage, two expert surgeons evaluated participants on both tasks before (Stage 1: Baseline) and immediately after training (Stage 1: Post-training) using a modified validated global rating scale of laparoscopic and robotic operative performance. In Stage 2, participants were evaluated on both tasks 11-20 weeks after training. Of the 40 students who participated in Stage 1, 23 (11 laparoscopic and 12 robotic) underwent repeat evaluation. During Stage 2, there were no significant differences between groups in objective or subjective measures for the laparoscopic task. Laparoscopic-trained participants' performances on the laparoscopic task were improved during Stage 2 compared to baseline measured by time to task completion, but not by the modified global rating scale. During the robotic task, the robotic-trained group demonstrated superior economy of motion (p = .017), Tissue Handling (p = .020), and fewer errors (p = .018) compared to the laparoscopic-trained group. Robotic skills acquisition from baseline with no significant deterioration as measured by modified global rating scale scores was observed among robotic-trained participants during Stage 2. Robotic skills acquired through simulation appear to be better maintained than laparoscopic simulation skills. This study is registered on ClinicalTrials.gov (NCT02370407).

A supramolecular miktoarm star polymer based on porphyrin metal complexation in water.

PubMed

Hou, Zhanyao; Dehaen, Wim; Lyskawa, Joël; Woisel, Patrice; Hoogenboom, Richard

2017-07-25

A novel supramolecular miktoarm star polymer was successfully constructed in water from a pyridine end-decorated polymer (Py-PmDEGA) and a metalloporphyrin based star polymer (ZnTPP-(PEG) 4 ) via metal-ligand coordination. The Py-PmDEGA moiety was prepared via a combination of reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequent aminolysis and Michael addition reactions to introduce the pyridine end-group. The ZnTPP(PEG) 4 star-polymer was synthesized by the reaction between tetrakis(p-hydroxyphenyl)porphyrin and toluenesulfonyl-PEG, followed by insertion of a zinc ion into the porphyrin core. The formation of a well-defined supramolecular AB 4 -type miktoarm star polymer was unambiguously demonstrated via UV-Vis spectroscopic titration, isothermal titration calorimetry (ITC) and diffusion ordered NMR spectroscopy (DOSY).

Evaluation of Novel Wet Chemistry Separation and Purification Methods to Facilitate Automation of Astatine-­211 Isolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilbur, Daniel Scott

This research is a collaborative effort between the research groups of the PIs, Dr. D. Scott Wilbur in the Department of Radiation Oncology at the University of Washington (UW) and Matthew O’Hara at the Pacific Northwest National Laboratory (PNNL). In this report only those studies conducted at UW and the budget information from UW will be reported. A separate progress and financial report will be provided by PNNL. This final report outlines the experiments (Tasks) conducted and results obtained at UW from July 1, 2013 thru June 30, 2016 (2-­year project with 1 year no-­cost extension). The report divides themore » information on the experiments and results obtained into the 5 specific objectives of the research efforts and the Tasks within those objectives. This format is used so that it is easy to see what has been accomplished in each area. A brief summary of the major findings from the studies is provided below. Summary of Major Findings from Research/Training Activities at UW: Anion and cation exchange columns did not provide adequate 211At capture and/or extraction results under conditions studied to warrant further evaluation; PEG-­Merrifield resins containing mPEG350, mPEG750, mPEG2000 and mPEG5000 were synthesized and evaluated; All of the mPEG resins with different sized mPEG moieties conjugated gave similar 211At capture (>95%) from 8M HCl solutions and release with conc. NH 4OH (~50-­80%), but very low quantities were released when NaOH was used as an eluent; Capture and release of 211At when loading [ 211At]astatate appeared to be similar to that of [ 211At]astatide on PEG columns, but further studies need to be conducted to confirm that; Capture of 211At on PEG columns was lower (e.g. 80-­90%) from solutions of 8M HNO 3, but higher capture rates (e.g. 99%) can be obtained when 10M HNO 3 is mixed with an equal quantity of 8M HCl; Addition of reductants to the 211At solutions did not appear to change the percent capture, but may have an effect on the % extracted; There was some indication that the PEG-­Merrifield resins could be saturated (perhaps with Bi) resulting in lower capture percentages, but more studies need to be done to confirm that; A target dissolution chamber, designed and built at PNNL, works well with syringe pumps so it can be used in an automated system; Preliminary semi-­automated 211At isolation studies have been conducted with full-scale target dissolution and 211At isolation using a PEG column on the Hamilton automated system gave low overall recoveries, but HNO 3 was used (rather than HCl) for loading the 211At and flow rates were not optimized; Results obtained using PEG columns are high enough to warrant further development on a fully automated system; Results obtained also indicate that additional studies are warranted to evaluate other types of columns for 211At separation from bismuth, which allow use of HNO 3/HCl mixtures for loading and NaOH for eluting 211At. Such a column could greatly simplify the overall isolation process and make it easier to automate.« less

pH-responsive supramolecular self-assembly of well-defined zwitterionic ABC miktoarm star terpolymers.

PubMed

Liu, Hao; Li, Changhua; Liu, Hewen; Liu, Shiyong

2009-04-21

We report the first example of the synthesis and pH-responsive supramolecular self-assembly of double hydrophilic ABC miktoarm star terpolymers. Well-defined ABC miktoarm star terpolymers consisting of poly(ethylene glycol), poly(tert-butyl methacrylate), and poly(2-(diethylamino)ethyl methacrylate) arms [PEG(-b-PtBMA)-b-PDEA] were synthesized via the combination of consecutive click reactions and atom transfer radical polymerization (ATRP), starting from a trifunctional core molecule, 1-azido-3-chloro-2-propanol (ACP). The click reaction of monoalkynyl-terminated PEG with an excess of ACP afforded difunctional PEG bearing a chlorine and a secondary hydroxyl moiety at the chain end, PEG113(-Cl)-OH (1). After azidation with NaN3, PEG-based macroinitiator PEG113(-N3)-Br (3) was prepared by the esterification of PEG113(-N3)-OH (2) with 2-bromoisobutyryl bromide and then employed in the ATRP of tert-butyl methacrylate (tBMA). The obtained PEG(-N3)-b-PtBMA copolymers (4) possessed an azido moiety at the diblock junction point. The preparation of PEG(-b-PtBMA)-b-PDEA miktoarm star terpolymers was then achieved via the click reaction of 4 with an excess of monoalkynyl-terminated PDEA. The obtained miktoarm star terpolymers were successfully converted into PEG(-b-PMAA)-b-PDEA, where PMAA is poly(methacrylic acid). In aqueous solution, PEG(-b-PMAA)-b-PDEA zwitterionic ABC miktoarm star terpolymers can self-assemble into three types of micellar aggregates by simply adjusting solution pH at room temperature. Above pH 8, PDEA-core micelles stabilized by PEG/ionized PMAA hybrid coronas were formed due to the insolubility of PDEA block. In the range of pH 5-7, micelles possessing polyion complex cores formed as a result of charge compensation between partially ionized PMAA and partially protonated PDEA sequences. At pH<4, hydrogen bonding interactions between fully protonated PMAA and PEG led to the formation of another type of micellar aggregates possessing hydrogen-bonded complex cores stabilized by protonated PDEA coronas. The fully reversible pH-responsive formation of three types of aggregates were characterized by 1H NMR, dynamic and static laser light scattering (LLS), and transmission electron microscopy (TEM).

Characterization of polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) as an MRI-visible vector for siRNA delivery in gastric cancer in vitro and in vivo.

PubMed

Chen, Yinting; Lian, Guoda; Liao, Chengde; Wang, Weiwei; Zeng, Linjuan; Qian, Chenchen; Huang, Kaihong; Shuai, Xintao

2013-07-01

Gene therapy is a promising therapeutic method but is severely hampered due to its lack of an ideal delivery system. Therefore, in this study, a nonviral and magnetic resonance imaging (MRI) visible vector, polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) was used as a nanocarrier for small interfering RNA (siRNA) delivery in gastric cancer. Biophysical characterization of PEG-g-PEI-SPION was systematically analyzed, including size, zeta potential, siRNA condensation capacity, cell viability, transfection efficiency, cellular uptake, and MRI-visible function in vivo. Besides, CD44 variant isoform 6 (CD44v6), a protein marker for metastatic behavior in gastric cancer, and was chose as the target gene to further analyze the siRNA delivery function of PEG-g-PEI-SPION. Under comprehensive analysis, the appropriate N/P ratio of PEG-g-PEI-SPION/siRNA was 10, and siRNA targeting at human CD44v6 (siCD44v6) transferred by PEG-g-PEI-SPION was effective at downregulating the CD44v6 expression of gastric carcinoma cell line SGC-7901 in vitro. Moreover, knockdown of CD44v6 impaired migrating and invasive abilities of SGC-7901 cells. Furthermore, PEG-g-PEI-SPION was a highly efficient contrast agent for MRI scan in vivo. PEG-g-PEI-SPION was a promising nonviral vector with molecular image tracing capacity for cancer gene therapy. And CD44v6 was a potential target gene for the prevention and detection of metastatic behavior in gastric cancer.

Unusual solvatochromic absorbance probe behaviour within mixtures of poly(ethylene glycol)-400 + ionic liquid, [bmim][Tf2N

NASA Astrophysics Data System (ADS)

Ali, Anwar; Ali, Maroof; Malik, Nisar Ahmad; Uzair, Sahar

2014-03-01

The potentially green solvents made up of ionic liquids (ILs) and poly(ethylene glycols) may have wide range of the applications in many chemical and biochemical fields. In the present work, solvatochromic absorbance probe behaviour is used to assess the physicochemical properties of the mixtures composed of PEG-400 + IL, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [bmim][Tf2N]. Lowest energy intramolecular charge-transfer absorbance maxima of a betaine dye, i.e., ETN , indicates the dipolarity/polarizability and/or hydrogen-bond donating (HBD) acidity of the [bmim][Tf2N] + PEG-400 mixtures to be even higher than that of neat [bmim][Tf2N], the solution component with higher dipolarity/polarizability and/or HBD acidity. Dipolarity/polarizability (π∗) obtained separately from the electronic absorbance response of probe N,N-diethyl-4-nitroaniline, and the HBD acidity (α) of PEG-400 + [bmim][Tf2N] mixtures are also observed to be anomalously high. A comparative study of the PEG + IL mixtures has also been done with PEG-400 + molecular organic solvents (protic polar [methanol], aprotic polar [N,N-dimethylformamide], and non polar, [benzene]) mixtures, but these mixtures do not show this type of unusual behaviour. A four-parameter simplified combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) equation is shown to satisfactorily predict the solvatochromic parameters within PEG-400 + different solvent mixtures.

Epigenetic analysis of bovine parthenogenetic embryonic fibroblasts.

PubMed

Kaneda, Masahiro; Takahashi, Masashi; Yamanaka, Ken-Ichi; Saito, Koji; Taniguchi, Masanori; Akagi, Satoshi; Watanabe, Shinya; Nagai, Takashi

2017-08-19

Although more than 100 imprinted genes have already been identified in the mouse and human genomes, little is known about genomic imprinting in cattle. For a better understanding of these genes in cattle, parthenogenetically activated bovine blastocysts were transferred to recipient cows to obtain parthenotes, and fibroblasts derived from a Day 40 (Day 0 being the day of parthenogenetic activation) parthenogenetic embryo (BpEFs) were successfully obtained. Bovine embryonic fibroblasts (BEFs) were also isolated from a normal fertilized embryo obtained from an artificially inseminated cow. The expression of imprinted genes was analyzed by RT-PCR. Paternally expressed genes (PEGs) in mouse (viz., IGF2, PEG3, ZAC1, NDN, DLK1, SGCE, and PEG10) were expressed in BEFs, but not in BpEFs, suggesting that these genes are also imprinted in cattle. However, other PEGs in mouse (viz., IMPACT, MAGEL2, SNRPN, and PEG1/MEST) were expressed in both BEFs and BpEFs. These genes may not be imprinted in BEFs. The expression of seven maternally expressed genes in mouse was also analyzed, and only CDKN1C was not expressed in BpEFs. The DNA methylation patterns of repetitive elements (Satellite I, Satellite II, alpha-satellite, and Art2) were not different between the BEFs and BpEFs; however, the differentially methylated region (DMR) of paternally methylated H19 was hypomethylated, whereas those of maternally methylated PEG3 and PEG10 were hypermethylated in BpEFs, as expected. The methylation of the SNRPN DMR was not different between the BEFs and BpEFs, in accordance with the SNRPN expression levels in both cell types. The XIST gene, which is essential for X chromosome inactivation in females, was expressed in BpEFs, whereas its DMR was half-methylated, suggesting that X chromosome inactivation is normal in these cells. Microarray analysis was also applied to identify novel PEGs that should be expressed only in BEFs but not in BpEFs. More than 300 PEG candidate genes, including IGF2, PEG3, and PEG10, were obtained. These results illustrate the epigenetic characteristic of bovine parthenogenetic embryos and contribute to the identification of novel imprinted genes in cattle.

Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus

PubMed Central

Dal Bosco, Lidiane; Weber, Gisele E.; Parfitt, Gustavo M.; Cordeiro, Arthur P.; Sahoo, Sangram K.; Fantini, Cristiano; Klosterhoff, Marta C.; Romano, Luis Alberto; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

2015-01-01

Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus. PMID:26075787

Blinking suppression of CdTe quantum dots on epitaxial graphene and the analysis with Marcus electron transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirose, Takuya; Tamai, Naoto, E-mail: tamai@kwansei.ac.jp; Kutsuma, Yasunori

We have prepared epitaxial graphene by a Si sublimation method from 4H-SiC. Single-particle spectroscopy of CdTe quantum dots (QDs) on epitaxial graphene covered with polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) showed the suppression of luminescence blinking and ∼10 times decreased luminescence intensity as compared with those on a glass. The electronic coupling constant, H{sub 01}, between CdTe QDs and graphene was calculated to be (3.3 ± 0.4) × 10{sup 2 }cm{sup −1} in PVP and (3.7 ± 0.8) × 10{sup 2 }cm{sup −1} in PEG based on Marcus theory of electron transfer and Tang-Marcus model of blinking with statistical distribution.

Artificial Versus Video-Based Immersive Virtual Surroundings: Analysis of Performance and User's Preference.

PubMed

Huber, Tobias; Paschold, Markus; Hansen, Christian; Lang, Hauke; Kneist, Werner

2018-06-01

Immersive virtual reality (VR) laparoscopy simulation connects VR simulation with head-mounted displays to increase presence during VR training. The goal of the present study was the comparison of 2 different surroundings according to performance and users' preference. With a custom immersive virtual reality laparoscopy simulator, an artificially created VR operating room (AVR) and a highly immersive VR operating room (IVR) were compared. Participants (n = 30) performed 3 tasks (peg transfer, fine dissection, and cholecystectomy) in AVR and IVR in a crossover study design. No overall difference in virtual laparoscopic performance was obtained when comparing results from AVR with IVR. Most participants preferred the IVR surrounding (n = 24). Experienced participants (n = 10) performed significantly better than novices (n = 10) in all tasks regardless of the surrounding ( P < .05). Participants with limited experience (n = 10) showed differing results. Presence, immersion, and exhilaration were significantly higher in IVR. Two thirds assumed that IVR would have a positive influence on their laparoscopic simulator use. This first study comparing AVR and IVR did not reveal differences in virtual laparoscopic performance. IVR is considered the more realistic surrounding and is therefore preferred by the participants.

More than a camera holder: teaching surgical skills to medical students.

PubMed

Abbas, Paulette; Holder-Haynes, Juliet; Taylor, Deborah J; Scott, Bradford G; Brandt, Mary L; Naik-Mathuria, Bindi

2015-05-15

Students often experience passive learning in their surgical rotations as they are delegated to holding the camera during laparoscopic cases. We introduced a laparoscopic skills course to medical students to provide hands-on experience. We hypothesized that the course will improve basic laparoscopic skills and increase interest in a surgical career. All students on the core surgery rotation attended two sessions in the surgical simulation laboratory lead by Department of Surgery faculty members. Surveys were used before and after the course to assess video game (VG) use and interest in a surgical career. Course effectiveness was assessed with a laparoscopic peg transfer exercise. One hundred one students participated with 82 students documenting preinstruction and postinstruction peg transfer times. There was an overall improvement in median transfer times after instruction (before 63 s [interquartile range {IQR} 46-84.5] versus after 50.5 s [IQR 39-65.2], P < 0.001). When stratified by gender, men (n = 40) had faster median preintervention peg transfer times than women (n = 61; 65 s [IQR 51-88]) versus 81 s [IQR 65-98] (P = 0.030). However, both genders had equivalent postinstruction transfer times (men 48 s [IQR 36-61] versus women 51.3 s [IQR 43.2-68.3], P = 0.478). A similar trend was observed between students with and without prior VG use. Of the 50 students who completed both surveys, there was no significant increase (pre-24% versus post-34%, P = 0.29) or decrease (pre-32% versus post-22%, P = 0.13) in interest in a surgical career after the course. A laparoscopic course for medical students is effective in improving laparoscopic skills. Although male gender and VG use may be associated with better intrinsic skills, instruction and practice allow female students and non-VG users to "catch up." A longer follow-up study is warranted to determine true interest in a surgical career. Copyright © 2015 Elsevier Inc. All rights reserved.

Comprehensive study of interaction between biocompatible PEG-InP/ZnS QDs and bovine serum albumin.

PubMed

Sannaikar, M S; Inamdar, Laxmi S; Pujar, G H; Wari, M N; Balasinor, Nafisa H; Inamdar, S R

2018-05-01

Polyethylene glycol (PEG) surface modified biocompatible InP/ZnS quantum dots (QDs) act as a potential alternative for conventional carcinogenic cadmium-based quantum dots for in vivo and in vitro studies. Comprehensively, we studied the interaction between a model protein bovine serum albumin (BSA) and PEGylated toxic free InP/ZnS QDs using various spectroscopic tools such as absorption, fluorescence quenching, time resolved and synchronous fluorescence spectroscopic measurements. These studies principally show that tryptophan (Trp) residues of BSA have preferable binding affinity towards PEG-InP/ZnS QDs surface and a blue shift in Trp fluorescence emission is a signature of conformational changes in its hydrophobic microenvironment. Photoluminescence (PL) intensity of Trp is quenched by ground state complex formation (static quenching) at room temperature. However, InP/ZnS@BSA conjugates become unstable with increasing temperature and PL intensity of Trp is quenched via dynamic quenching by PEG-InP/ZnS QDs. Experimentally determined thermodynamic parameters for these conjugates have shown spontaneity, entropy driven and exothermic nature of bio-conjugation. The calculated binding affinity (n ≅ 1, Hill coefficient) suggest that the affinity of InP/ZnS QDs for a BSA protein is not dependent on whether or not other BSA proteins are already bound to the QD surface. Energy transfer efficiency (E), Trp residue to InP/ZnS QDs distances and energy transfer rate (k T ) were all obtained from FÖrster resonance energy. Copyright © 2017 John Wiley & Sons, Ltd.

Monolayer-protected clusters of gold nanoparticles: impacts of stabilizing ligands on the heterogeneous electron transfer dynamics and voltammetric detection.

PubMed

Pillay, Jeseelan; Ozoemena, Kenneth I; Tshikhudo, Robert T; Moutloali, Richard M

2010-06-01

Surface electrochemistry of novel monolayer-protected gold nanoparticles (MPCAuNPs) is described. Protecting ligands, (1-sulfanylundec-11-yl)tetraethylene glycol (PEG-OH) and (1-sulfanylundec-11-yl)poly(ethylene glycol)ic acid (PEG-COOH), of three different percent ratios (PEG-COOH:PEG-OH), 1:99 (MPCAuNP-COOH(1%)), 50:50 (MPCAuNP-COOH(50%)), and 99:1 (MPCAuNP-COOH(99%)), were studied. The electron transfer rate constants (k(et)/s(-1)) in organic medium decreased as the concentration of the surface-exposed -COOH group in the protecting monolayer ligand is increased: MPCAuNP-COOH(1%) (approximately 5 s(-1)) > MPCAuNP-COOH(50%) (approximately 4 s(-1)) > MPCAuNP-COOH(99%) (approximately 0.5 s(-1)). In aqueous medium, the trend is reversed. The surface pK(a) was estimated as approximately 8.2 for the MPCAuNP-COOH(1%), while both MPCAuNP-COOH(50%) and MPCAuNP-COOH(99%) showed two pK(a) values of about 5.0 and approximately 8.0. These results have been interpreted in terms of the quasi-solidity and quasi-liquidity of the terminal -OH and -COOH head groups, respectively. MPCAuNP-COOH(99%) excellently suppressed the voltammetric response of the ascorbic acid but enhanced the electrocatalytic detection of epinephrine compared to the other MPCAuNPs studied. This study reveals important factors that should be considered when designing electrode devices that employ monolayer-protected gold nanoparticles and possibly for some other redox-active metal nanoparticles.

Core-shell microstructured nanocomposites for synergistic adjustment of environmental temperature and humidity

NASA Astrophysics Data System (ADS)

Zhang, Haiquan; Yuan, Yanping; Zhang, Nan; Sun, Qingrong; Cao, Xiaoling

2016-11-01

The adjustment of temperature and humidity is of great importance in a variety of fields. Composites that can perform both functions are prepared by mixing phase change materials (PCMs) with hygroscopic materials. However, the contact area between the adsorbent and humid air is inevitably decreased in such structures, which reduces the number of mass transfer channels for water vapor. An approach entailing the increase in the mass ratio of the adsorbent is presented here to improve the adsorption capacity. A core-shell CuSO4/polyethylene glycol (PEG) nanomaterial was developed to satisfy the conflicting requirements of temperature control and dehumidification. The results show that the equilibrium adsorption capacity of the PEG coating layer was enhanced by a factor of 188 compared with that of the pure PEG powder. The coating layer easily concentrates vapor, providing better adsorption properties for the composite. Furthermore, the volume modification of the CuSO4 matrix was reduced by 80% by the PEG coated layer, a factor that increases the stability of the composite. For the phase change process, the crystallization temperature of the coating layer was adjusted between 37.2 and 46.3 °C by interfacial tension. The core-shell CuSO4/PEG composite reported here provides a new general approach for the simultaneous control of temperature and humidity.

Evaluation of Augmented Reality Feedback in Surgical Training Environment.

PubMed

Zahiri, Mohsen; Nelson, Carl A; Oleynikov, Dmitry; Siu, Ka-Chun

2018-02-01

Providing computer-based laparoscopic surgical training has several advantages that enhance the training process. Self-evaluation and real-time performance feedback are 2 of these advantages, which avoid dependency of trainees on expert feedback. The goal of this study was to investigate the use of a visual time indicator as real-time feedback correlated with the laparoscopic surgical training. Twenty novices participated in this study working with (and without) different presentations of time indicators. They performed a standard peg transfer task, and their completion times and muscle activity were recorded and compared. Also of interest was whether the use of this type of feedback induced any side effect in terms of motivation or muscle fatigue. Of the 20 participants, 15 (75%) preferred using a time indicator in the training process rather than having no feedback. However, time to task completion showed no significant difference in performance with the time indicator; furthermore, no significant differences in muscle activity or muscle fatigue were detected with/without time feedback. The absence of significant difference between task performance with/without time feedback shows that using visual real-time feedback can be included in surgical training based on user preference. Trainees may benefit from this type of feedback in the form of increased motivation. The extent to which this can influence training frequency leading to performance improvement is a question for further study.

Synthesis of mesoporous β-Ga2O3 nanorods using PEG as template: preparation, characterization and photocatalytic properties.

PubMed

Zhao, Weirong; Yang, Yong; Hao, Rui; Liu, Feifei; Wang, Yan; Tan, Min; Tang, Jing; Ren, Daqing; Zhao, Dongye

2011-09-15

Mesoporous wide bandgap semiconductors offer high photocatalytic oxidation and mineralization activities. In this study, mesoporous β-Ga(2)O(3) diamond nanorods with 200-300 nm in diameter and 1.0-1.2 μm in length were synthesized via a urea-based hydrothermal method using polyethylene glycol (PEG) as template agent. The UV photocatalytic oxidation activity of β-Ga(2)O(3) for gaseous toluene was evaluated, and 7 kinds of intermediates were monitored online by a proton transfer reaction mass spectrometry. Photoluminescence spectra manifested that the dosage and molecular weight of PEG are crucial for formation of vacancies and photocatalytic oxidation activities. A PEG-assisted hydrothermal formation mechanism of mesoporous β-Ga(2)O(3) diamond nanorods was proposed. Based on the health risk influence index (η) of the intermediates, the calculated health risks revealed that the β-Ga(2)O(3) nanorods with a η value of 9.6 are much safer than TiO(2) (η = 17.6). Copyright © 2011 Elsevier B.V. All rights reserved.

Combining hard and soft magnetism into a single core-shell nanoparticle to achieve both hyperthermia and image contrast

PubMed Central

Yang, Qiuhong; Gong, Maogang; Cai, Shuang; Zhang, Ti; Douglas, Justin T; Chikan, Viktor; Davies, Neal M; Lee, Phil; Choi, In-Young; Ren, Shenqiang; Forrest, M Laird

2015-01-01

Background A biocompatible core/shell structured magnetic nanoparticles (MNPs) was developed to mediate simultaneous cancer therapy and imaging. Methods & results A 22-nm MNP was first synthesized via magnetically coupling hard (FePt) and soft (Fe3O4) materials to produce high relative energy transfer. Colloidal stability of the FePt@Fe3O4 MNPs was achieved through surface modification with silane-polyethylene glycol (PEG). Intravenous administration of PEG-MNPs into tumor-bearing mice resulted in a sustained particle accumulation in the tumor region, and the tumor burden of treated mice was a third that of the mice in control groups 2 weeks after a local hyperthermia treatment. In vivo magnetic resonance imaging exhibited enhanced T2 contrast in the tumor region. Conclusion This work has demonstrated the feasibility of cancer theranostics with PEG-MNPs. PMID:26606855

Proficiency training on a virtual reality robotic surgical skills curriculum.

PubMed

Bric, Justin; Connolly, Michael; Kastenmeier, Andrew; Goldblatt, Matthew; Gould, Jon C

2014-12-01

The clinical application of robotic surgery is increasing. The skills necessary to perform robotic surgery are unique from those required in open and laparoscopic surgery. A validated laparoscopic surgical skills curriculum (Fundamentals of Laparoscopic Surgery or FLS™) has transformed the way surgeons acquire laparoscopic skills. There is a need for a similar skills training and assessment tool for robotic surgery. Our research group previously developed and validated a robotic training curriculum in a virtual reality (VR) simulator. We hypothesized that novice robotic surgeons could achieve proficiency levels defined by more experienced robotic surgeons on the VR robotic curriculum, and that this would result in improved performance on the actual daVinci Surgical System™. 25 medical students with no prior robotic surgery experience were recruited. Prior to VR training, subjects performed 2 FLS tasks 3 times each (Peg Transfer, Intracorporeal Knot Tying) using the daVinci Surgical System™ docked to a video trainer box. Task performance for the FLS tasks was scored objectively. Subjects then practiced on the VR simulator (daVinci Skills Simulator) until proficiency levels on all 5 tasks were achieved before completing a post-training assessment of the 2 FLS tasks on the daVinci Surgical System™ in the video trainer box. All subjects to complete the study (1 dropped out) reached proficiency levels on all VR tasks in an average of 71 (± 21.7) attempts, accumulating 164.3 (± 55.7) minutes of console training time. There was a significant improvement in performance on the robotic FLS tasks following completion of the VR training curriculum. Novice robotic surgeons are able to attain proficiency levels on a VR simulator. This leads to improved performance in the daVinci surgical platform on simulated tasks. Training to proficiency on a VR robotic surgery simulator is an efficient and viable method for acquiring robotic surgical skills.

Robotics training program: evaluation of the satisfaction and the factors that influence success of skills training in a resident robotics curriculum.

PubMed

Lucas, Steven M; Gilley, David A; Joshi, Shreyas S; Gardner, Thomas A; Sundaram, Chandru P

2011-10-01

We present our experience of training residents in a weekend robotic training program to assess its effectiveness and perceived usefulness. Bimonthly training sessions were arranged such that residents could sign up for hour-long, weekend training sessions. They are required to complete four training sessions. Five tasks were scored for time and accuracy: Peg-Board, checkerboard, string running, pattern cutting, and suturing. Participants completed surveys (5-point Likert scale) regarding program utility, ease of attendance, and interest in future weekend training sessions. Mean number of trials completed by 19 residents was >4, and 16 completed the trials within an average of 13.7±8.1 mos. Significant improvements (P<0.05) were seen in final trials for Peg-Board accuracy (95.8% vs 79.0%), checkerboard deviation (4.8% vs 18.2%), and time (293 s vs 404 s), pattern-cutting time (257 s vs 399 s), and suture time (203 s vs 305 s). Time to previous session correlated with relative improvement in Peg-Board and pattern-cutting time (r=0.300 and 0.277, P=0.021 and 0.041), but no specific training interval was predictive of improvement. Residents found the course easy to attend (3.6), noted skills improvement (4.1), and found it useful (4.0). Training in the weekend sessions improved performance of basic tasks on the robot. Training interval had a modest effect on some exercises and may be more important for difficult tasks. This training program is a useful supplement to resident training and would be easy to implement in most programs.

Polyethylene Glycol Polymers in Low Volume Resuscitation

DTIC Science & Technology

2017-10-01

peripheral vascular disease and chronic heart failure, and space medicine. What as the impact on technology transfer? Technology transfer is a very...patterns were almost identical in volunteers and trauma patients. The significantly lower clot strength in blood diluted with 10% PEG-20k could be...lost in the US, compared to cancer (16%), heart disease (12%), and HIV (2%) (1). For all traumatic injuries, hemorrhagic shock is responsible for

Acquisition and retention of laparoscopic skills is different comparing conventional laparoscopic and single-incision laparoscopic surgery: a single-centre, prospective randomized study.

PubMed

Ellis, Scott Michael; Varley, Martin; Howell, Stuart; Trochsler, Markus; Maddern, Guy; Hewett, Peter; Runge, Tina; Mees, Soeren Torge

2016-08-01

Training in laparoscopic surgery is important not only to acquire and improve skills but also avoid the loss of acquired abilities. The aim of this single-centre, prospective randomized study was to assess skill acquisition of different laparoscopic techniques and identify the point in time when acquired skills deteriorate and training is needed to maintain these skills. Sixty surgical novices underwent laparoscopic surgery (LS) and single-incision laparoscopic surgery (SILS) baseline training (BT) performing two validated tasks (peg transfer, precision cutting). The novices were randomized into three groups and skills retention testing (RT) followed after 8 (group A), 10 (group B) or 12 (group C) weeks accordingly. Task performance was measured in time with time penalties for insufficient task completion. 92 % of the participants completed the BT and managed to complete the task in the required time frame of proficiency. Univariate and multivariate analyses revealed that SILS (P < 0.0001) and precision cutting (P < 0.0001) were significantly more difficult. Males performed significantly better than females (P < 0.005). For LS, a deterioration of skills (comparison of BT vs RT) was not identified; however, for SILS a significant deterioration of skills (adjustment of BT and RT values) was demonstrated for all groups (A-C) (P < 0.05). Our data reveal that complex laparoscopic tasks (cutting) and techniques (SILS) are more difficult to learn and acquired skills more difficult to maintain. Acquired LS skills were maintained for the whole observation period of 12 weeks but SILS skills had begun to deteriorate at 8 weeks. These data show that maintenance of LS and SILS skills is divergent and training curricula need to take these specifics into account.

Insight into fast ion migration kinetics of a new hybrid single Li-ion conductor based on aluminate complexes for solid-state Li-ion batteries.

PubMed

Feng, Yancong; Tan, Rui; Zhao, Yan; Gao, Rongtan; Yang, Luyi; Yang, Jinlong; Li, Hao; Zhou, Guofu; Chen, Haibiao; Pan, Feng

2018-03-29

A novel hybrid single Li-ion conductor (SLIC) for a Li-ion solid electrolyte was prepared by mixing aluminate complexes-polyethylene glycol (LiAl-PEG) and polyethylene oxide (PEO) for solid-state Li-ion batteries. The LiAl-PEG/PEO blend possesses high thermal stability and electrochemical stability with an oxidation decomposition voltage up to 4.8 V. Notably, this hybrid SLIC exhibits not only excellent Li-ion migration kinetics, but also good ionic conductivity as high as 4.0 × 10-5 and 2.6 × 10-4 S cm-1 at 30 and 100 °C, respectively, which is much higher than previously reported SLICs. Importantly, by the combination of molecular dynamics simulations and experiment measurements, the mechanisms of Li-ion migration across the SLIC (LiAl-PEG), the salt-in-polymer (LiClO4/PEO) and the optimized SLIC (LiAl-PEG/PEO) were systematically investigated for the first time. The new hopping transport mechanism was verified for the SLIC system at the nanoscale. As for the hybrid SLIC, PEO chains enhance the segmental mobility of the ether-chains bonded with Al atoms, improve the ionicity, and provide extra ionic paths for Li transfer, resulting in the optimized Li-ion migration kinetics of LiAl-PEG/PEO.

Random coil negative control reproduces the discrepancy between scattering and FRET measurements of denatured protein dimensions

PubMed Central

Watkins, Herschel M.; Simon, Anna J.; Sosnick, Tobin R.; Lipman, Everett A.; Hjelm, Rex P.; Plaxco, Kevin W.

2015-01-01

Small-angle scattering studies generally indicate that the dimensions of unfolded single-domain proteins are independent (to within experimental uncertainty of a few percent) of denaturant concentration. In contrast, single-molecule FRET (smFRET) studies invariably suggest that protein unfolded states contract significantly as the denaturant concentration falls from high (∼6 M) to low (∼1 M). Here, we explore this discrepancy by using PEG to perform a hitherto absent negative control. This uncharged, highly hydrophilic polymer has been shown by multiple independent techniques to behave as a random coil in water, suggesting that it is unlikely to expand further on the addition of denaturant. Consistent with this observation, small-angle neutron scattering indicates that the dimensions of PEG are not significantly altered by the presence of either guanidine hydrochloride or urea. smFRET measurements on a PEG construct modified with the most commonly used FRET dye pair, however, produce denaturant-dependent changes in transfer efficiency similar to those seen for a number of unfolded proteins. Given the vastly different chemistries of PEG and unfolded proteins and the significant evidence that dye-free PEG is well-described as a denaturant-independent random coil, this similarity raises questions regarding the interpretation of smFRET data in terms of the hydrogen bond- or hydrophobically driven contraction of the unfolded state at low denaturant. PMID:25964362

Simultaneous CCD Photometry of Two Eclipsing Binary Stars in Pegasus - Part2: BX Peg

NASA Astrophysics Data System (ADS)

Alton, K. B.

2013-05-01

BX Peg is an overcontact W UMa binary system (P = 0.280416 d) which has been rather well studied, but not fully understood due to complex changes in eclipse timings and light curve variations attributed to star spots. Photometric data collected in three bandpasses (B, V, and Ic) produced nineteen new times of minimum for BX Peg. These were used to update the linear ephemeris and further analyze potential changes in orbital periodicity by examining long-term changes in eclipse timings. In addition, synthetic fitting of light curves by Roche modeling was accomplished with the assistance of three different programs, two of which employ the Wilson-Devinney code. Different spotted solutions were necessary to achieve the best Roche model fits for BX Peg light curves collected in 2008 and 2011. Overall, the long-;term decrease (9.66 × 10-3 sec y-1) in orbital period defined by the parabolic fit of eclipse timing data could arise from mass transfer or angular momentum loss. The remaining residuals from observed minus predicted eclipse timings for BX Peg exhibit complex but non-random behavior. These may be related to magnetic activity cycles and/or the presence of an unseen mass influencing the times of minimum, however, additional minima need to be collected over a much longer timescale to resolve the nature of these complex changes.

Core-shell microstructured nanocomposites for synergistic adjustment of environmental temperature and humidity

PubMed Central

Zhang, Haiquan; Yuan, Yanping; Zhang, Nan; Sun, Qingrong; Cao, Xiaoling

2016-01-01

The adjustment of temperature and humidity is of great importance in a variety of fields. Composites that can perform both functions are prepared by mixing phase change materials (PCMs) with hygroscopic materials. However, the contact area between the adsorbent and humid air is inevitably decreased in such structures, which reduces the number of mass transfer channels for water vapor. An approach entailing the increase in the mass ratio of the adsorbent is presented here to improve the adsorption capacity. A core-shell CuSO4/polyethylene glycol (PEG) nanomaterial was developed to satisfy the conflicting requirements of temperature control and dehumidification. The results show that the equilibrium adsorption capacity of the PEG coating layer was enhanced by a factor of 188 compared with that of the pure PEG powder. The coating layer easily concentrates vapor, providing better adsorption properties for the composite. Furthermore, the volume modification of the CuSO4 matrix was reduced by 80% by the PEG coated layer, a factor that increases the stability of the composite. For the phase change process, the crystallization temperature of the coating layer was adjusted between 37.2 and 46.3 °C by interfacial tension. The core-shell CuSO4/PEG composite reported here provides a new general approach for the simultaneous control of temperature and humidity. PMID:27845371

Polyethylene glycol promotes autoxidation of cytochrome c.

PubMed

Sato, Wataru; Uchida, Takeshi; Saio, Tomohide; Ishimori, Koichiro

2018-06-01

Cytochrome c (Cyt c) was rapidly oxidized by molecular oxygen in the presence, but not absence of PEG. The redox potential of heme c was determined by the potentiometric titration to be +236 ± 3 mV in the absence of PEG, which was negatively shifted to +200 ± 4 mV in the presence of PEG. The underlying the rapid oxidation was explored by examining the structural changes in Cyt c in the presence of PEG using UV-visible absorption, circular dichroism, resonance Raman, and fluorescence spectroscopies. These spectroscopic analyses suggested that heme oxidation was induced by a modest tertiary structural change accompanied by a slight shift in the heme position (<1.0 Å) rather than by partial denaturation, as is observed in the presence of cardiolipin. The near-infrared spectra showed that PEG induced dehydration from Cyt c, which triggered heme displacement. The primary dehydration site was estimated to be around surface-exposed hydrophobic residues near the heme center: Ile81 and Val83. These findings and our previous studies, which showed that hydrated water molecules around Ile81 and Val83 are expelled when Cyt c forms a complex with CcO, proposed that dehydration of these residues is functionally significant to electron transfer from Cyt c to CcO. Copyright © 2018 Elsevier B.V. All rights reserved.

Association between fine motor skills and binocular visual function in children with reading difficulties.

PubMed

Niechwiej-Szwedo, Ewa; Alramis, Fatimah; Christian, Lisa W

2017-12-01

Performance of fine motor skills (FMS) assessed by a clinical test battery has been associated with reading achievement in school-age children. However, the nature of this association remains to be established. The aim of this study was to assess FMS in children with reading difficulties using two experimental tasks, and to determine if performance is associated with reduced binocular function. We hypothesized that in comparison to an age- and sex-matched control group, children identified with reading difficulties will perform worse only on a motor task that has been shown to rely on binocular input. To test this hypothesis, motor performance was assessed using two tasks: bead-threading and peg-board in 19 children who were reading below expected grade and age-level. Binocular vision assessment included tests for stereoacuity, fusional vergence, amplitude of accommodation, and accommodative facility. In comparison to the control group, children with reading difficulties performed significantly worse on the bead-threading task. In contrast, performance on the peg-board task was similar in both groups. Accommodative facility was the only measure of binocular function significantly associated with motor performance. Findings from our exploratory study suggest that normal binocular vision may provide an important sensory input for the optimal development of FMS and reading. Given the small sample size tested in the current study, further investigation to assess the contribution of binocular vision to the development and performance of FMS and reading is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Spherical Tippe Tops

NASA Astrophysics Data System (ADS)

Cross, Rod

2013-03-01

A tippe top (see Fig. 1) is usually constructed as a truncated sphere with a cylindrical peg on top, as indicated in Fig. 2(a). When spun rapidly on a horizontal surface, a tippe top spins about a vertical axis while rotating slowly about a horizontal axis until the peg touches the surface. At that point, weight is transferred to the peg, the truncated sphere rises off the surface, and the top spins on the peg until it is upright. A feature of a tippe top is that its center of mass, labeled G in Fig. 2, is below the geometric center of the sphere, C, when the top is at rest. That is where it will return if the top is tilted sideways and released since that is the stable equilibrium position. The fact that a tippe top turns upside down when it spins is therefore astonishing. The behavior of a tippe top is quite unlike that of a regular top since the spin axis remains closely vertical the whole time. The center of mass of a regular top can also rise, but the spin axis tilts upward as the top rises and enters a "sleeping" position.

Spontaneous transfer of stearic acids between human serum albumin and PEG:2000-grafted DPPC membranes.

PubMed

Pantusa, Manuela; Stirpe, Andrea; Sportelli, Luigi; Bartucci, Rosa

2010-05-01

Electron spin resonance (ESR) spectroscopy is used to study the transfer of stearic acids between human serum albumin (HSA) and sterically stabilized liposomes (SSL) composed of dipalmitoylphosphatidylcholine (DPPC) and of submicellar content of poly(ethylene glycol:2000)-dipalmitoylphosphatidylethanolamine (PEG:2000-DPPE). Protein/lipid dispersions are considered in which spin-labelled stearic acids at the 16th carbon atom along the acyl chain (16-SASL) are inserted either in the protein or in the SSL. Two component ESR spectra with different rotational mobility are obtained over a broad range of temperature and membrane composition. Indeed, superimposed to an anisotropic protein-signal, appears a more isotropic lipid-signal. Since in the samples only one matrix (protein or membranes) is spin-labelled, the other component accounts for the transfer of 16-SASL between albumin and membranes. The two components have been resolved and quantified by spectral subtractions, and the fraction, f (p) (16-SASL), of spin labels bound non-covalently to the protein has been used to monitor the transfer. It is found that it depends on the type of donor and acceptor matrix, on the physical state of the membranes and on the grafting density of the polymer-lipids. Indeed, it is favoured from SSL to HSA and the fraction of stearic acids transferred increases with temperature in both directions of transfer. Moreover, in the presence of polymer-lipids, the transfer from HSA to SSL is slightly attenuated, especially in the brush regime of the polymer-chains. Instead, the transfer from SSL to HSA is favoured by the polymer-lipids much more in the mushroom than in the brush regime.

Use of Collapsible Box Trainer as a Module for Resident Education

PubMed Central

Caban, Angel M.; Guido, Christopher; Silver, Michele; Rossidis, George; Sarosi, George

2013-01-01

Background and Objectives: We sought to determine whether training with a simple collapsible mobile box trainer leads to improved performance of fundamental laparoscopic skills (FLSs) during a 6-month interval versus validated laparoscopic box trainers and virtual-reality trainers, only accessible at a simulation training center. Methods: With institutional review board approval, 20 first- and second-year general surgery residents were randomized to scheduled training sessions in a surgical simulation laboratory or training in the use of a portable, collapsible Train Anywhere Skill Kit (TASKit) (Ethicon Endo-Surgery Cincinnati, OH, USA) trainer. Training was geared toward the FLS set for a skill assessment examination at a 6-month interval. Results: The residents who trained with the TASKit performed the peg-transfer, pattern-cut exercise, Endoloop, and intracorporeal knot-tying FLS tasks statistically more efficiently during their 6-month assessment versus their initial evaluation as compared with the group randomized to the simulation laboratory training. Conclusions: Using a simple collapsible mobile box trainer such as the TASKit can be a cost-effective method of training and preparing residents for FLS tasks considering the current cost associated with virtual and high-definition surgical trainers. This mode of surgical training allows residents to practice in their own time by removing barriers associated with simulation centers. PMID:24018083

Investigation on the improvement and transfer of dual-task coordination skills.

PubMed

Strobach, Tilo; Frensch, Peter A; Soutschek, Alexander; Schubert, Torsten

2012-11-01

Recent research has demonstrated that dual-task performance in situations with two simultaneously presented tasks can be substantially improved with extensive practice. This improvement was related to the acquisition of task coordination skills. Earlier studies provided evidence that these skills result from hybrid practice, including dual and single tasks, but not from single-task practice. It is an open question, however, whether task coordination skills are independent from the specific practice situation and are transferable to new situations or whether they are non-transferable and task-specific. The present study, therefore, tested skill transfer in (1) a dual-task situation with identical tasks in practice and transfer, (2) a dual-task situation with two tasks changed from practice to transfer, and (3) a task switching situation with two sequentially presented tasks. Our findings are largely consistent with the assumption that task coordination skills are non-transferable and task-specific. We cannot, however, definitively reject the assumption of transferable skills when measuring error rates in the dual-task situation with two changed tasks after practice. In the task switching situation, single-task and hybrid practice both led to a transfer effect on mixing costs.

The transfer of skills from cognitive and physical training to activities of daily living: a randomised controlled study.

PubMed

Hagovska, Magdalena; Nagyova, Iveta

2017-06-01

Ageing is associated with the deterioration of all cognitive functions, including attention, memory and psychomotor speed. It has not yet been clearly confirmed whether the effects of cognitive and physical interventions can improve activities of daily living (ADL). This study compared the effectiveness of cognitive and physical training on cognitive functions and the transfer to ADL. Eighty older people with mild cognitive impairment (mean age 67.07 ± 4.3 years) were randomly divided into an experimental group ( n  = 40) and a control group ( n  = 40). Data were collected in an outpatient psychiatric clinic in a randomised controlled trial. Primary outcome measures included the following: cognitive functions were evaluated using the mini mental state examination, the AVLT-Auditory verbal learning test, the Stroop test, the TMT-trail making test, the DRT-disjunctive reaction time and the NHPT-nine hole peg test. Secondary outcome measure was the Bristol activities of daily living scale. The experimental group underwent a CogniPlus and physical training; consisting of 20 training sessions over 10 weeks. Both groups went through 30 min of daily physical training for 10 weeks. After the training, significant differences in favour of the experimental group were found in almost all the tests. In memory (AVLT) (p ≤ 0.0001, effect size (ES) η 2  = 0.218. In reduction of the response time on attention tasks (Stroop tasks) ( p  ≤ 0.006, ES = 0.092-0.115). In lower error rates in all tests: Stroop tasks, DRT, TMT, NHPT ( p  ≤ 0.02-0.001, ES = 0.062-0.176). In ADL ( p  ≤ 0.0001, ES = 0.176). The combined cognitive and physical training had better efficacy for most cognitive functions and for ADL when compared with the physical training only.

Laparoscopic assistance by operating room nurses: Results of a virtual-reality study.

PubMed

Paschold, M; Huber, T; Maedge, S; Zeissig, S R; Lang, H; Kneist, W

2017-04-01

Laparoscopic assistance is often entrusted to a less experienced resident, medical student, or operating room nurse. Data regarding laparoscopic training for operating room nurses are not available. The aim of the study was to analyse the initial performance level and learning curves of operating room nurses in basic laparoscopic surgery compared with medical students and surgical residents to determine their ability to assist with this type of procedure. The study was designed to compare the initial virtual reality performance level and learning curves of user groups to analyse competence in laparoscopic assistance. The study subjects were operating room nurses, medical students, and first year residents. Participants performed three validated tasks (camera navigation, peg transfer, fine dissection) on a virtual reality laparoscopic simulator three times in 3 consecutive days. Laparoscopic experts were enrolled as a control group. Participants filled out questionnaires before and after the course. Nurses and students were comparable in their initial performance (p>0.05). Residents performed better in camera navigation than students and nurses and reached the expert level for this task. Residents, students, and nurses had comparable bimanual skills throughout the study; while, experts performed significantly better in bimanual manoeuvres at all times (p<0.05). The included user groups had comparable skills for bimanual tasks. Residents with limited experience reached the expert level in camera navigation. With training, nurses, students, and first year residents are equally capable of assisting in basic laparoscopic procedures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Histidine-rich stabilized polyplexes for cMet-directed tumor-targeted gene transfer

NASA Astrophysics Data System (ADS)

Kos, Petra; Lächelt, Ulrich; Herrmann, Annika; Mickler, Frauke Martina; Döblinger, Markus; He, Dongsheng; Krhač Levačić, Ana; Morys, Stephan; Bräuchle, Christoph; Wagner, Ernst

2015-03-01

Overexpression of the hepatocyte growth factor receptor/c-Met proto oncogene on the surface of a variety of tumor cells gives an opportunity to specifically target cancerous tissues. Herein, we report the first use of c-Met as receptor for non-viral tumor-targeted gene delivery. Sequence-defined oligomers comprising the c-Met binding peptide ligand cMBP2 for targeting, a monodisperse polyethylene glycol (PEG) for polyplex surface shielding, and various cationic (oligoethanamino) amide cores containing terminal cysteines for redox-sensitive polyplex stabilization, were assembled by solid-phase supported syntheses. The resulting oligomers exhibited a greatly enhanced cellular uptake and gene transfer over non-targeted control sequences, confirming the efficacy and target-specificity of the formed polyplexes. Implementation of endosomal escape-promoting histidines in the cationic core was required for gene expression without additional endosomolytic agent. The histidine-enriched polyplexes demonstrated stability in serum as well as receptor-specific gene transfer in vivo upon intratumoral injection. The co-formulation with an analogous PEG-free cationic oligomer led to a further compaction of pDNA polyplexes with an obvious change of shape as demonstrated by transmission electron microscopy. Such compaction was critically required for efficient intravenous gene delivery which resulted in greatly enhanced, cMBP2 ligand-dependent gene expression in the distant tumor.Overexpression of the hepatocyte growth factor receptor/c-Met proto oncogene on the surface of a variety of tumor cells gives an opportunity to specifically target cancerous tissues. Herein, we report the first use of c-Met as receptor for non-viral tumor-targeted gene delivery. Sequence-defined oligomers comprising the c-Met binding peptide ligand cMBP2 for targeting, a monodisperse polyethylene glycol (PEG) for polyplex surface shielding, and various cationic (oligoethanamino) amide cores containing terminal cysteines for redox-sensitive polyplex stabilization, were assembled by solid-phase supported syntheses. The resulting oligomers exhibited a greatly enhanced cellular uptake and gene transfer over non-targeted control sequences, confirming the efficacy and target-specificity of the formed polyplexes. Implementation of endosomal escape-promoting histidines in the cationic core was required for gene expression without additional endosomolytic agent. The histidine-enriched polyplexes demonstrated stability in serum as well as receptor-specific gene transfer in vivo upon intratumoral injection. The co-formulation with an analogous PEG-free cationic oligomer led to a further compaction of pDNA polyplexes with an obvious change of shape as demonstrated by transmission electron microscopy. Such compaction was critically required for efficient intravenous gene delivery which resulted in greatly enhanced, cMBP2 ligand-dependent gene expression in the distant tumor. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06556e

Outcome of Rehabilitation and Swallowing Therapy after Percutaneous Endoscopic Gastrostomy in Dysphagia Patients.

PubMed

Toh Yoon, Ezekiel Wong; Hirao, Jun; Minoda, Naoko

2016-12-01

The objective of this study was to investigate the outcomes of rehabilitation (with swallowing therapy) after percutaneous endoscopic gastrostomy (PEG) in patients with neurogenic dysphagia. Forty-seven patients (29 males and 18 females) who were transferred to the rehabilitation ward of our hospital after receiving PEG tube placements during a 5-year period were enrolled in this study. Patients' demographic data, comorbidities, nutritional statuses, and laboratory biomarkers before the PEG procedure were collected. Rehabilitation (with swallowing therapy) outcomes such as changes in Functional Independence Measure (FIM) and dysphagia grade (using Fujishima's classification) were evaluated. Significant improvements in FIM scores and dysphagia grades after rehabilitation therapy were observed. Twenty-seven patients (57.4 %) were discharged with some oral intake and 10 patients (21.3%) were discharged PEG-free (defined as the PEG tube not being used or removed). Factors associated with being discharged with some oral intake were increase in FIM score (adjusted OR 1.10, 95 % CI 1.02-1.19) and higher baseline dysphagia grade (adjusted OR 1.88, 95 % CI 1.04-3.39). Factors associated with being discharged PEG-free were longer rehabilitation period (OR 1.03, 95 % CI 1.01-1.04), absence of respiratory disorders (OR 0.12, 95 % CI 0.03-0.35), and increase in FIM score (OR 1.17, 95 % CI 1.08-1.28). Changes in dysphagia grade were significantly correlated with changes in FIM score (r 2  = 0.46, p < 0.0001), indicating that improvement of FIM scores through general rehabilitation therapy may play an important role in the treatment of dysphagia.

Effect of PEG-PDMAEMA Block Copolymer Architecture on Polyelectrolyte Complex Formation with Heparin.

PubMed

Välimäki, Salla; Khakalo, Alexey; Ora, Ari; Johansson, Leena-Sisko; Rojas, Orlando J; Kostiainen, Mauri A

2016-09-12

Heparin is a naturally occurring polyelectrolyte consisting of a sulfated polysaccharide backbone. It is widely used as an anticoagulant during major surgical operations. However, the associated bleeding risks require rapid neutralization after the operation. The only clinically approved antidote for heparin is protamine sulfate, which is, however, ineffective against low molecular weight heparin and can cause severe adverse reactions in patients. In this study, the facile synthesis of cationic-neutral diblock copolymers and their effective heparin binding is presented. Poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PDMAEMA) block copolymers were synthesized in two steps via atom-transfer radical polymerization (ATRP) using PEG as a macroinitiator. Solution state binding between heparin and a range of PEG-PDMAEMA block copolymers and one homopolymer was studied with dynamic light scattering and methylene blue displacement assay. Also in vitro binding in plasma was studied by utilizing a chromogenic heparin anti-Xa assay. Additionally, quartz crystal microbalance and multiparametric surface plasmon resonance were used to study the surface adsorption kinetics of the polymers on a heparin layer. It was shown that the block copolymers and heparin form electrostatically bound complexes with varying colloidal properties, where the block lengths play a key role in controlling the heparin binding affinity, polyelectrolyte complex size and surface charge. With the optimized polymers (PEG114PDMAEMA52 and PEG114PDMAEMA100), heparin could be neutralized in a dose-dependent manner, and bound efficiently into small neutral complexes, with a hydrodynamic radius less than 100 nm. These complexes had only a limited effect on cell viability. Based on these studies, our approach paves the way for the development of new polymeric heparin binding agents.

Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies

NASA Astrophysics Data System (ADS)

Yan, Xuefeng; Hu, Hao; Lin, Jing; Jin, Albert J.; Niu, Gang; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

2015-01-01

Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves the fluorescence of loaded DVDMS via intramolecular charge transfer. Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of GO for improved PA imaging and PTT. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This novel theranostics is well suited for fluorescence/PA dual-modal imaging and synergistic PDT/PTT.

On the adsorption properties of magnetic fluids: Impact of bulk structure

NASA Astrophysics Data System (ADS)

Kubovcikova, Martina; Gapon, Igor V.; Zavisova, Vlasta; Koneracka, Martina; Petrenko, Viktor I.; Soltwedel, Olaf; Almasy, László; Avdeev, Mikhail V.; Kopcansky, Peter

2017-04-01

Adsorption of nanoparticles from magnetic fluids (MFs) on solid surface (crystalline silicon) was studied by neutron reflectometry (NR) and related to the bulk structural organization of MFs concluded from small-angle neutron scattering (SANS). The initial aqueous MF with nanomagnetite (co-precipitation reaction) stabilized by sodium oleate and MF modified by a biocompatible polymer, poly(ethylene glycol) (PEG), were considered. Regarding the bulk structure it was confirmed in the SANS experiment that comparatively small and compact (size 30 nm) aggregates of nanoparticle in the initial sample transfer to large and developed (size>130 nm, fractal dimension 2.7) associates in the PEG modified MF. This reorganization in the aggregates correlates with the changes in the neutron reflectivity that showed that a single adsorption layer of individual nanoparticles on the oxidized silicon surface for the initial MF disappears after the PEG modification. It is concluded that all particles in the modified fluid are in the aggregates that are not adsorbed by silicon.

Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles

PubMed Central

Mui, Barbara L; Tam, Ying K; Jayaraman, Muthusamy; Ansell, Steven M; Du, Xinyao; Tam, Yuen Yi C; Lin, Paulo JC; Chen, Sam; Narayanannair, Jayaprakash K; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Akinc, Akin; Maier, Martin A; Cullis, Pieter; Madden, Thomas D; Hope, Michael J

2013-01-01

Lipid nanoparticles (LNPs) encapsulating short interfering RNAs that target hepatic genes are advancing through clinical trials, and early results indicate the excellent gene silencing observed in rodents and nonhuman primates also translates to humans. This success has motivated research to identify ways to further advance this delivery platform. Here, we characterize the polyethylene glycol lipid (PEG-lipid) components, which are required to control the self-assembly process during formation of lipid particles, but can negatively affect delivery to hepatocytes and hepatic gene silencing in vivo. The rate of transfer from LNPs to plasma lipoproteins in vivo is measured for three PEG-lipids with dialkyl chains 14, 16, and 18 carbons long. We show that 1.5 mol % PEG-lipid represents a threshold concentration at which the chain length exerts a minimal effect on hepatic gene silencing but can still modify LNPs pharmacokinetics and biodistribution. Increasing the concentration to 2.5 and 3.5 mol % substantially compromises hepatocyte gene knockdown for PEG-lipids with distearyl (C18) chains but has little impact for shorter dimyristyl (C14) chains. These data are discussed with respect to RNA delivery and the different rates at which the steric barrier disassociates from LNPs in vivo. PMID:24345865

Force-Sensing Enhanced Simulation Environment (ForSense) for laparoscopic surgery training and assessment.

PubMed

Cundy, Thomas P; Thangaraj, Evelyn; Rafii-Tari, Hedyeh; Payne, Christopher J; Azzie, Georges; Sodergren, Mikael H; Yang, Guang-Zhong; Darzi, Ara

2015-04-01

Excessive or inappropriate tissue interaction force during laparoscopic surgery is a recognized contributor to surgical error, especially for robotic surgery. Measurement of force at the tool-tissue interface is, therefore, a clinically relevant skill assessment variable that may improve effectiveness of surgical simulation. Popular box trainer simulators lack the necessary technology to measure force. The aim of this study was to develop a force sensing unit that may be integrated easily with existing box trainer simulators and to (1) validate multiple force variables as objective measurements of laparoscopic skill, and (2) determine concurrent validity of a revised scoring metric. A base plate unit sensitized to a force transducer was retrofitted to a box trainer. Participants of 3 different levels of operative experience performed 5 repetitions of a peg transfer and suture task. Multiple outcome variables of force were assessed as well as a revised scoring metric that incorporated a penalty for force error. Mean, maximum, and overall magnitudes of force were significantly different among the 3 levels of experience, as well as force error. Experts were found to exert the least force and fastest task completion times, and vice versa for novices. Overall magnitude of force was the variable most correlated with experience level and task completion time. The revised scoring metric had similar predictive strength for experience level compared with the standard scoring metric. Current box trainer simulators can be adapted for enhanced objective measurements of skill involving force sensing. These outcomes are significantly influenced by level of expertise and are relevant to operative safety in laparoscopic surgery. Conventional proficiency standards that focus predominantly on task completion time may be integrated with force-based outcomes to be more accurately reflective of skill quality. Copyright © 2015 Elsevier Inc. All rights reserved.

Value of fundamentals of laparoscopic surgery training in a fourth-year medical school advanced surgical skills elective.

PubMed

Edelman, David A; Mattos, Mark A; Bouwman, David L

2012-10-01

Few data are available describing the benefits of initiating fundamentals of laparoscopic surgery (FLS) training during medical school. We hypothesized that an intense 1-month surgical skills elective that included FLS task training for fourth-year medical students (MS4s) would result in performance levels indistinguishable from graduating chief residents (PGY5) who had received clinical skill training and access to self-guided FLS curriculum. From July 2007 through June 2011, 114 MS4s participated in a 1-month advanced surgical skills elective. The curriculum for the elective included cadaver dissections, patient management presentations, and surgical skill training (open surgical skills and basic laparoscopic skills modules performed on FLS trainers and virtual reality laparoscopic simulators). From June 2009 through June 2011, 21 PGY5s graduated who had never received formalized FLS skills training. These residents were tested on FLS by a certified proctor and the results recorded. The performance outcome measure was task completion time. Unpaired Student's t-test was used to compare the performance measures for each group. All PGY5s achieved FLS certification on their first attempt and completed enough cases for graduation. The MS4 group showed significantly better performance than the PGY5 group in the peg transfer and circle cut (P < 0.05). No difference was seen in the knot tying tasks between the two groups (P > 0.05) Incorporating FLS training into a 1 month-long medical school surgery elective enabled MS4s to achieve FLS performance similar to, or better than, the performance achieved by PGY5 surgery residents. We support the integration of FLS skills task training as a standard part of the skills training curriculum for medical students. Copyright © 2012 Elsevier Inc. All rights reserved.

Telerobotic control of a dextrous manipulator using master and six-DOF hand-controllers for space assembly and servicing tasks

NASA Technical Reports Server (NTRS)

O'Hara, John M.

1987-01-01

Two studies were conducted evaluating methods of controlling a telerobot; bilateral force reflecting master controllers and proportional rate six degrees of freedom (DOF) hand controllers. The first study compared the controllers on performance of single manipulator arm tasks, a peg-in-the-hole task, and simulated satellite orbital replacement unit changeout. The second study, a Space Station truss assembly task, required simultaneous operation of both manipulator arms (all 12 DOFs) and complex multiaxis slave arm movements. Task times were significantly longer and fewer errors were committed with the hand controllers. The hand controllers were also rated significantly higher in cognitive and manual control workload on the two-arm task. The master controllers were rated significantly higher in physical workload. There were no significant differences in ratings of manipulator control quality.

Relationship of Preschool Academic Skill Deficits to Subsequent Acquisition of Reading and Mathematic Skills.

ERIC Educational Resources Information Center

Morrow, Robert D.; McBride, Hugh J.

This article discusses the assessment of language and cognitive development as reflected in preschool activities and describes the Preschool Language-Cognitive Assessment for Curriculum Entry (PLACE). Five task-skill areas associated with common preschool activities (building with blocks, completing puzzles, pounding pegs, etc) are identified. How…

Skills in minimally invasive and open surgery show limited transferability to robotic surgery: results from a prospective study.

PubMed

Kowalewski, Karl-Friedrich; Schmidt, Mona W; Proctor, Tanja; Pohl, Moritz; Wennberg, Erica; Karadza, Emir; Romero, Philipp; Kenngott, Hannes G; Müller-Stich, Beat P; Nickel, Felix

2018-04-01

There is limited evidence on the transferability of conventional laparoscopic and open surgical skills to robotic-assisted surgery. The primary aim of this study was to evaluate the transferability of expertise in conventional laparoscopy and open surgery to robotic-assisted surgery using the da Vinci Skills Simulator (dVSS). Secondary aims included evaluating the influence of individual participants' characteristics. Participants performed four tasks on the dVSS: Peg Board 1 (PB), Pick and Place (PP), Thread the Rings (TR), and Suture Sponge 1 (SS). Participants were classified into three groups (Novice, Intermediate, Experts) according to experience in laparoscopic and open surgery. All tasks were performed twice except for SS. Performance was assessed using the built-in scoring system. 37 medical students and 25 surgeons participated. Experts did not perform significantly better than less experienced participants on the dVSS. Specifically, with regard to laparoscopic experience, total simulator scores were: Novices 68.2 ± 28.8; Intermediates 65.1 ± 31.2; Experts 65.1 ± 30.0; p = 0.611. Regarding open surgical experience, scores were: Novices 68.6 ± 28.7; Intermediates 68.2 ± 30.8; Experts 63.2 ± 30.3; p = 0.305. Although there were some significant differences among groups for single parameters in specific tasks, there was no constant superiority of one group. Laparoscopic and open surgical Novices improved significantly in overall score and time for all three tasks (p < 0.05). Laparoscopic intermediates improved only in PP time (4.64 ± 3.42; p = 0.006), open Intermediates in PB score (11.98 ± 13.01; p = 0.025), and open Experts in PP score (6.69 ± 11.48; p = 0.048). Laparoscopic experts showed no improvement. Participants with gaming experience had better overall scores than non-gamers when comparing all second attempts (Gamer 83.62 ± 7.57; Non-Gamer 76.31 ± 12.78; p = 0.008) as well as first and second attempts together (Gamer 72.08 ± 8.86; Non-Gamer 65.45 ± 11.68; p = 0.039). Musical and sports experience showed no correlation with robotic performance. Robotic-assisted surgery requires skills distinct from conventional laparoscopy or open surgery. Basic robotic skills training prior to patient contact should be required.

Manipulating flexible parts using a teleoperated system with time delay: An experiment

NASA Technical Reports Server (NTRS)

Kotoku, T.; Takamune, K.; Tanie, K.; Komoriya, K.; Matsuhira, N.; Asakura, M.; Bamba, H.

1994-01-01

This paper reports experiments involving the handling of flexible parts (e.g. wires) when using a teleoperated system with time delay. The task is principally a peg-in-hole task involving the wrapping of a wire around two posts on the task-board. It is difficult to estimate the effects of the flexible parts; therefore, on-line teleoperation is indispensable for this class of unpredictable task. We first propose a teleoperation system based on the predictive image display, then describe an experimental teleoperation testbed with a four second transmission time delay. Finally, we report on wire handling operations that were performed to evaluate the performance of this system. Those experiments will contribute to future advanced experiments for the MITI ETS-7 mission.

A serious game skills competition increases voluntary usage and proficiency of a virtual reality laparoscopic simulator during first-year surgical residents' simulation curriculum.

PubMed

El-Beheiry, Mostafa; McCreery, Greig; Schlachta, Christopher M

2017-04-01

The objective of this study was to assess the effect of a serious game skills competition on voluntary usage of a laparoscopic simulator among first-year surgical residents' standard simulation curriculum. With research ethics board approval, informed consent was obtained from first-year surgical residents enrolled in an introductory surgical simulation curriculum. The class of 2013 served as a control cohort following the standard curriculum which mandates completion of six laparoscopic simulator skill tasks. For the 2014 competition cohort, the only change introduced was the biweekly and monthly posting of a leader board of the top three and ten fastest peg transfer times. Entry surveys were administered assessing attitudes towards simulation-based training and competition. Cohorts were observed for 5 months. There were 24 and 25 residents in the control and competition cohorts, respectively. The competition cohort overwhelmingly (76 %) stated that they were not motivated to deliberate practice by competition. Median total simulator usage time was 132 min (IQR = 214) in the competition cohort compared to 89 (IQR = 170) in the control cohort. The competition cohort completed their course requirements significantly earlier than the control cohort (χ 2  = 6.5, p = 0.01). There was a significantly greater proportion of residents continuing to use the simulator voluntarily after completing their course requirements in the competition cohort (44 vs. 4 %; p = 0.002). Residents in the competition cohort were significantly faster at peg transfer (194 ± 66 vs. 233 ± 53 s, 95 % CI of difference = 4-74 s; p = 0.03) and significantly decreased their completion time by 33 ± 54 s (95 % CI 10-56 s; paired t test, p = 0.007). A simple serious games skills competition increased voluntary usage and performance on a laparoscopic simulator, despite a majority of participants reporting they were not motivated by competition. Future directions should endeavour to examine other serious gaming modalities to further engage trainees in simulated skills development.

Transfer in motion perceptual learning depends on the difficulty of the training task.

PubMed

Wang, Xiaoxiao; Zhou, Yifeng; Liu, Zili

2013-06-07

One hypothesis in visual perceptual learning is that the amount of transfer depends on the difficulty of the training and transfer tasks (Ahissar & Hochstein, 1997; Liu, 1995, 1999). Jeter, Dosher, Petrov, and Lu (2009), using an orientation discrimination task, challenged this hypothesis by arguing that the amount of transfer depends only on the transfer task but not on the training task. Here we show in a motion direction discrimination task that the amount of transfer indeed depends on the difficulty of the training task. Specifically, participants were first trained with either 4° or 8° direction discrimination along one average direction. Their transfer performance was then tested along an average direction 90° away from the trained direction. A variety of transfer measures consistently demonstrated that transfer performance depended on whether the participants were trained on 4° or 8° directional difference. The results contradicted the prediction that transfer was independent of the training task difficulty.

An investigation of response and stimulus modality transfer effects after dual-task training in younger and older.

PubMed

Lussier, Maxime; Gagnon, Christine; Bherer, Louis

2012-01-01

It has been shown that dual-task training leads to significant improvement in dual-task performance in younger and older adults. However, the extent to which training benefits to untrained tasks requires further investigation. The present study assessed (a) whether dual-task training leads to cross-modality transfer in untrained tasks using new stimuli and/or motor responses modalities, (b) whether transfer effects are related to improved ability to prepare and maintain multiple task-set and/or enhanced response coordination, (c) whether there are age-related differences in transfer effects. Twenty-three younger and 23 older adults were randomly assigned to dual-task training or control conditions. All participants were assessed before and after training on three dual-task transfer conditions; (1) stimulus modality transfer (2) response modality transfer (3) stimulus and response modalities transfer task. Training group showed larger improvement than the control group in the three transfer dual-task conditions, which suggests that training leads to more than specific learning of stimuli/response associations. Attentional costs analyses showed that training led to improved dual-task cost, only in conditions that involved new stimuli or response modalities, but not both. Moreover, training did not lead to a reduced task-set cost in the transfer conditions, which suggests some limitations in transfer effects that can be expected. Overall, the present study supports the notion that cognitive plasticity for attentional control is preserved in late adulthood.

Coupled enzyme reactions performed in heterogeneous reaction media: experiments and modeling for glucose oxidase and horseradish peroxidase in a PEG/citrate aqueous two-phase system.

PubMed

Aumiller, William M; Davis, Bradley W; Hashemian, Negar; Maranas, Costas; Armaou, Antonios; Keating, Christine D

2014-03-06

The intracellular environment in which biological reactions occur is crowded with macromolecules and subdivided into microenvironments that differ in both physical properties and chemical composition. The work described here combines experimental and computational model systems to help understand the consequences of this heterogeneous reaction media on the outcome of coupled enzyme reactions. Our experimental model system for solution heterogeneity is a biphasic polyethylene glycol (PEG)/sodium citrate aqueous mixture that provides coexisting PEG-rich and citrate-rich phases. Reaction kinetics for the coupled enzyme reaction between glucose oxidase (GOX) and horseradish peroxidase (HRP) were measured in the PEG/citrate aqueous two-phase system (ATPS). Enzyme kinetics differed between the two phases, particularly for the HRP. Both enzymes, as well as the substrates glucose and H2O2, partitioned to the citrate-rich phase; however, the Amplex Red substrate necessary to complete the sequential reaction partitioned strongly to the PEG-rich phase. Reactions in ATPS were quantitatively described by a mathematical model that incorporated measured partitioning and kinetic parameters. The model was then extended to new reaction conditions, i.e., higher enzyme concentration. Both experimental and computational results suggest mass transfer across the interface is vital to maintain the observed rate of product formation, which may be a means of metabolic regulation in vivo. Although outcomes for a specific system will depend on the particulars of the enzyme reactions and the microenvironments, this work demonstrates how coupled enzymatic reactions in complex, heterogeneous media can be understood in terms of a mathematical model.

Effects of PEG-induced osmotic stress on growth and dhurrin levels of forage sorghum.

PubMed

O'Donnell, Natalie H; Møller, Birger Lindberg; Neale, Alan D; Hamill, John D; Blomstedt, Cecilia K; Gleadow, Roslyn M

2013-12-01

Sorghum (Sorghum bicolor L. Moench) is a valuable forage crop in regions with low soil moisture. Sorghum may accumulate high concentrations of the cyanogenic glucoside dhurrin when drought stressed resulting in possible cyanide (HCN) intoxication of grazing animals. In addition, high concentrations of nitrate, also potentially toxic to ruminants, may accumulate during or shortly after periods of drought. Little is known about the degree and duration of drought-stress required to induce dhurrin accumulation, or how changes in dhurrin concentration are influenced by plant size or nitrate metabolism. Given that finely regulating soil moisture under controlled conditions is notoriously difficult, we exposed sorghum plants to varying degrees of osmotic stress by growing them for different lengths of time in hydroponic solutions containing polyethylene glycol (PEG). Plants grown in medium containing 20% PEG (-0.5 MPa) for an extended period had significantly higher concentrations of dhurrin in their shoots but lower dhurrin concentrations in their roots. The total amount of dhurrin in the shoots of plants from the various treatments was not significantly different on a per mass basis, although a greater proportion of shoot N was allocated to dhurrin. Following transfer from medium containing 20% PEG to medium lacking PEG, shoot dhurrin concentrations decreased but nitrate concentrations increased to levels potentially toxic to grazing ruminants. This response is likely due to the resumption of plant growth and root activity, increasing the rate of nitrate uptake. Data presented in this article support a role for cyanogenic glucosides in mitigating oxidative stress. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Development of facile drug delivery platform of ranibizumab fabricated PLGA-PEGylated magnetic nanoparticles for age-related macular degeneration therapy.

PubMed

Yan, Jian; Peng, Xifeng; Cai, Yulian; Cong, Wendong

2018-06-01

The present anti-angiogenic therapies for neovascular age-related macular degeneration require effective drug delivery systems for transfer drug molecules. Ranibizumab is an active humanized monoclonal antibody that counteracts active forms of vascular endothelial growth factor A in the neovascular age-related macular degeneration therapy. The development of ranibizumab-related therapies, we have designed the effective drug career with engineered magnetic nanoparticles (Fe 3 O 4 ) as a facile platform of ranibizumab delivery for the treatment of neovascular age-related macular degeneration. Ranibizumab conjugated iron oxide (Fe 3 O 4 )/PEGylated poly lactide-co-glycolide (PEG-PLGA) was successfully designed and the synthesized materials are analyzed different analytical techniques. The microscopic techniques (Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM)) are clearly displayed that spherical nanoparticles into the PEG-PLGA matrix and presence of elements and chemical interactions confirmed by the results of energy dispersive X-ray analysis (EDX) and Fourier trans-form infrared (FTIR) spectroscopic methods. The in vitro anti-angiogenic evaluation of Fe 3 O 4 /PEG-PLGA polymer nanomaterial efficiently inhibits the tube formation in the Matrigel-based assay method by using human umbilical vein endothelial cells. Ranibizumab treated Fe 3 O 4 /PEG-PLGA polymer nanomaterials not disturbed cell proliferation and the results could not display the any significant differences in human endothelial cells. The present investigated results describe that Fe 3 O 4 /PEG-PLGA polymer nanomaterials can be highly favorable and novel formulation for the treatment of neovascular age-related macular degeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Fine Motor Differences and Prenatal Serotonin Reuptake Inhibitors Exposure.

PubMed

Partridge, Marie-Claire A E; Salisbury, Amy L; LaGasse, Linda L

2016-08-01

To examine fine motor differences between preschoolers with prenatal exposure to serotonin reuptake inhibitor (SRI) and children of mothers with major depressive disorder. A subset of children (N = 40) from a larger study on the effects of prenatal SRI and untreated major depressive disorder participated in a kinematic task of visual motor and fine motor functions at ages 4-5 years: exposure to SRI (n = 15), untreated major depressive disorder exposure (n = 10), and the control group (n = 15). The task was to reach and secure a peg, then drop it in a small hole near the start position in the light condition with full visibility or in the glow condition in which a phosphorescent peg glows in the dark. Movement-tracking software measured the positioning of the moving hand and fingers. In the glow condition, the group exposed to SRIs had a greater proportion of maximum aperture than the group with major depressive disorder, and the group exposed to SRIs was slower than the group with major depressive disorder to drop the peg into the hole. In the glow condition, the trajectory of the group exposed to SRI was less straight than the group with major depressive disorder, and the group with major depressive disorder had a straighter trajectory than the control group. This study provides evidence that preschool aged children with prenatal SRI exposure have poorer fine motor and visual-motor control compared with those with prenatal untreated major depressive disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

The Perceived Efficacy and Goal Setting System (PEGS), part II: evaluation of test-retest reliability and differences between child and parental reports in the Swedish version.

PubMed

Vroland-Nordstrand, Kristina; Krumlinde-Sundholm, Lena

2012-11-01

to evaluate the test-retest reliability of children's perceptions of their own competence in performing daily tasks and of their choice of goals for intervention using the Swedish version of the perceived efficacy and goal setting system (PEGS). A second aim was to evaluate agreement between children's and parents' perceptions of the child's competence and choices of intervention goals. Forty-four children with disabilities and their parents completed the Swedish version of the PEGS. Thirty-six of the children completed a retest session allocated into one of two groups: (A) for evaluation of perceived competence and (B) for evaluation of choice of goals. Cohen's kappa, weighted kappa and absolute agreement were calculated. Test-retest reliability for children's perceived competence showed good agreement for the dichotomized scale of competent/non-competent performance; however, using the four-point scale the agreement varied. The children's own goals were relatively stable over time; 78% had an absolute agreement ranging from 50% to 100%. There was poor agreement between the children's and their parents' ratings. Goals identified by the children differed from those identified by their parents, with 48% of the children having no goals identical to those chosen by their parents. These results indicate that the Swedish version of the PEGS produces reliable outcomes comparable to the original version.

New dimensions in surgical training: immersive virtual reality laparoscopic simulation exhilarates surgical staff.

PubMed

Huber, Tobias; Paschold, Markus; Hansen, Christian; Wunderling, Tom; Lang, Hauke; Kneist, Werner

2017-11-01

Virtual reality (VR) and head mount displays (HMDs) have been advanced for multimedia and information technologies but have scarcely been used in surgical training. Motion sickness and individual psychological changes have been associated with VR. The goal was to observe first experiences and performance scores using a new combined highly immersive virtual reality (IVR) laparoscopy setup. During the study, 10 members of the surgical department performed three tasks (fine dissection, peg transfer, and cholecystectomy) on a VR simulator. We then combined a VR HMD with the VR laparoscopic simulator and displayed the simulation on a 360° video of a laparoscopic operation to create an IVR laparoscopic simulation. The tasks were then repeated. Validated questionnaires on immersion and motion sickness were used for the study. Participants' times for fine dissection were significantly longer during the IVR session (regular: 86.51 s [62.57 s; 119.62 s] vs. IVR: 112.35 s [82.08 s; 179.40 s]; p = 0.022). The cholecystectomy task had higher error rates during IVR. Motion sickness did not occur at any time for any participant. Participants experienced a high level of exhilaration, rarely thought about others in the room, and had a high impression of presence in the generated IVR world. This is the first clinical and technical feasibility study using the full IVR laparoscopy setup combined with the latest laparoscopic simulator in a 360° surrounding. Participants were exhilarated by the high level of immersion. The setup enables a completely new generation of surgical training.

Factors associated with simulator-assessed laparoscopic surgical skills of veterinary students.

PubMed

Kilkenny, Jessica J; Singh, Ameet; Kerr, Carolyn L; Khosa, Deep K; Fransson, Boel A

2017-06-01

OBJECTIVE To determine whether simulator-assessed laparoscopic skills of veterinary students were associated with training level and prior experience performing nonlaparoscopic veterinary surgery and other activities requiring hand-eye coordination and manual dexterity. DESIGN Experiment. SAMPLE 145 students without any prior laparoscopic surgical or fundamentals of laparoscopic surgery (FLS) simulator experience in years 1 (n = 39), 2 (34), 3 (39), and 4 (33) at a veterinary college. PROCEDURES A questionnaire was used to collect data from participants regarding experience performing veterinary surgery, playing video games, and participating in other activities. Participants performed a peg transfer, pattern cutting, and ligature loop-placement task on an FLS simulator, and FLS scores were assigned by an observer. Scores were compared among academic years, and correlations between amounts of veterinary surgical experience and FLS scores were assessed. A general linear model was used to identify predictors of FLS scores. RESULTS Participants were predominantly female (75%), right-hand dominant (92%), and between 20 and 29 years of age (98%). No significant differences were identified among academic years in FLS scores for individual tasks or total FLS score. Scores were not significantly associated with prior surgical or video game experience. Participants reporting no handicraft experience had significantly lower total FLS scores and FLS scores for task 2 than did participants reporting a lot of handicraft experience. CONCLUSIONS AND CLINICAL RELEVANCE Prior veterinary surgical and video game experience had no influence on FLS scores in this group of veterinary students, suggesting that proficiency of veterinary students in FLS may require specific training.

Synthesis and characterization of nanomagnetite particles and their polymer coated forms.

PubMed

Utkan, Guldem Guven; Sayar, Filiz; Batat, Pinar; Ide, Semra; Kriechbaum, Manfred; Pişkin, Erhan

2011-01-15

Superparamagnetic nanoparticles were prepared by coprecipitation of ferrous (Fe(2+)) and ferric (Fe(3+)) aqueous solution by a base. Nanomagnetite particles were coated with poly(St/PEG-EEM/DMAPM) and poly(St/PEG-MA/DMAPM) layer by emulsifier-free emulsion polymerization. Chemical structure of nanoparticles was characterized by both FTIR and (1)H NMR. Particle morphologies were determined by Zeta Sizer, DLS, XRD and SAXS. Structural analysis showed that after polymer coating nanomagnetite particles kept their superparamagnetic property. Besides the synthesized magnetites, polymer coated forms of these particles are more biocompatible, well dispersable and uniform. These properties make them a very strong candidate for bioengineering applications, such as bioseparation, gene transfer. Copyright © 2010 Elsevier Inc. All rights reserved.

Pharmacokinetics and behavioral effects of liposomal hydromorphone suitable for perioperative use in rhesus macaques

PubMed Central

KuKanich, Butch; Schmidt, Brynn; Heath, Timothy D.; Brown, Carolyn

2011-01-01

Introduction This study aims to evaluate the pharmacokinetic, behavioral, and motor effects of a liposomal preparation of hydromorphone hydrochloride (LE-hydro) in rhesus monkeys. We administered either 2 mg/kg of LE-hydro (n=8) subcutaneous (s.c.) or 0.1 mg/kg of standard pharmaceutical hydromorphone HCl (hydro) preparation either intravenous (i.v.; n=4) or s.c. (n=5). Materials and methods Serial blood samples were drawn after injection and analyzed for serum hydro concentration by liquid chromatography/mass spectrometry. Following s.c. injection of 0.1 mg/kg hydro or 2 mg/kg LE-hydro, behavioral evaluations were conducted in groups of rhesus monkeys (n=10/group) in the presence of a compatible stimulus animal and motor skills were also evaluated (n=10/group). The motor skills test consisted of removing a food reward (carrot ring) from either a straight peg (simple task) or a curved peg (difficult task). Results LE-hydro (MRT0-INF = 105.9 h) demonstrated extended-release pharmacokinetics compared to hydro when administered by either i.v. (MRT0-INF =1.1 h) or s.c. (MRT0-INF =1.3 h) routes. Hydro did not affect motor performance of the simpler task, but the monkeys’ performance deteriorated on the more difficult task at 0.5 and 1 h after injection. LE-hydro had no effect on motor skills in either the simpler or more difficult task. Conclusions The results of these studies indicate that LE-hydro has a pharmacokinetic and behavioral side effects profile consistent with an analgesic that could be tested for surgical use in animals. Our studies also expand the use of rhesus monkeys as a translational behavioral pharmacodynamics model for testing extended-release opioid medication. PMID:21404039

Chemical modification of protein A chromatography ligands with polyethylene glycol. I: Effects on IgG adsorption equilibrium, kinetics, and transport.

PubMed

Weinberg, Justin; Zhang, Shaojie; Crews, Gillian; Carta, Giorgio; Przybycien, Todd

2018-04-20

Chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) has been proposed as a strategy to increase the process selectivity and resin robustness by providing the ligand with a steric repulsion barrier against non-specific binding. This article comprises a comprehensive study of IgG adsorption and transport in Repligen CaptivA PriMAB resin with PEGylated ProA ligands that are modified using 5.2 and 21.5 kDa PEG chains. We studied the impact of the molecular weight of the PEG as well as the extent of PEGylation for the 5.2 kDa PEG modification. In all cases, PEGylation of ProA ligands decreases the resin average pore size, particle porosity, and static binding capacity for IgG proportional to the volume of conjugated PEG in the resin. Resin batch uptake experiments conducted in bulk via a stirred-tank system and with individual resin particles under confocal laser scanning microscopy suggests that PEGylation introduces heterogeneity into IgG binding kinetics: a fraction of the IgG binding sites are transformed from typical fast association kinetic behavior to slow kinetic behavior. pH gradient elution experiments of an IgG molecule on the modified resins show an increase in IgG elution pH for all modified resins, implying a decrease in IgG-ProA binding affinity on modification. Despite losses in static binding capacity for all resins with PEGylated ligands, the loss of dynamic binding capacity at 10% breakthrough (DBC 10% ) ranged more broadly from almost 0-47% depending on the PEG molecular weight and the extent of PEGylation. Minimal losses in DBC 10% were observed with a low extent of PEGylation with a smaller molecular weight PEG, while higher losses were observed at higher extents of PEGylation and with higher molecular weight PEG due to decreased static binding capacity and increased mass transfer resistance. This work provides insight into the practical implications for resin performance if PEGylation is considered as a strategy for selectivity enhancement in affinity chromatography with macromolecular ligands. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of virtual reality training on functional reaching movements in people with Parkinson's disease: a randomized controlled pilot trial.

PubMed

Ma, Hui-Ing; Hwang, Wen-Juh; Fang, Jing-Jing; Kuo, Jui-Kun; Wang, Ching-Yi; Leong, Iat-Fai; Wang, Tsui-Ying

2011-10-01

To investigate whether practising reaching for virtual moving targets would improve motor performance in people with Parkinson's disease. Randomized pretest-posttest control group design. A virtual reality laboratory in a university setting. Thirty-three adults with Parkinson's disease. The virtual reality training required 60 trials of reaching for fast-moving virtual balls with the dominant hand. The control group had 60 practice trials turning pegs with their non-dominant hand. Pretest and posttest required reaching with the dominant hand to grasp real stationary balls and balls moving at different speeds down a ramp. Success rates and kinematic data (movement time, peak velocity and percentage of movement time for acceleration phase) from pretest and posttest were recorded to determine the immediate transfer effects. Compared with the control group, the virtual reality training group became faster (F = 9.08, P = 0.005) and more forceful (F = 9.36, P = 0.005) when reaching for real stationary balls. However, there was no significant difference in success rate or movement kinematics between the two groups when reaching for real moving balls. A short virtual reality training programme improved the movement speed of discrete aiming tasks when participants reached for real stationary objects. However, the transfer effect was minimal when reaching for real moving objects.

Transferability of Dual-Task Coordination Skills after Practice with Changing Component Tasks

PubMed Central

Schubert, Torsten; Liepelt, Roman; Kübler, Sebastian; Strobach, Tilo

2017-01-01

Recent research has demonstrated that dual-task performance with two simultaneously presented tasks can be substantially improved as a result of practice. Among other mechanisms, theories of dual-task practice-relate this improvement to the acquisition of task coordination skills. These skills are assumed (1) to result from dual-task practice, but not from single-task practice, and (2) to be independent from the specific stimulus and response mappings during the practice situation and, therefore, transferable to new dual task situations. The present study is the first that provides an elaborated test of these assumptions in a context with well-controllable practice and transfer situations. To this end, we compared the effects of dual-task and single-task practice with a visual and an auditory sensory-motor component task on the dual-task performance in a subsequent transfer session. Importantly, stimulus and stimulus-response mapping conditions in the two component tasks changed repeatedly during practice sessions, which prevents that automatized stimulus-response associations may be transferred from practice to transfer. Dual-task performance was found to be improved after practice with the dual tasks in contrast to the single-task practice. These findings are consistent with the assumption that coordination skills had been acquired, which can be transferred to other dual-task situations independently on the specific stimulus and response mapping conditions of the practiced component tasks. PMID:28659844

Mechanisms underlying transfer of task-defined rules across feature dimensions.

PubMed

Baroni, Giulia; Yamaguchi, Motonori; Chen, Jing; Proctor, Robert W

2013-01-01

The Simon effect can be reversed, favoring spatially noncorresponding responses, when people respond to stimulus colors (e.g., green) by pressing a key labeled with the alternative color (i.e., red). This Hedge and Marsh reversal is most often attributed to transfer of logical recoding rules from the color dimension to the location dimension. A recent study showed that this transfer of logical recoding rules can occur not only within a single task but also across two separate tasks that are intermixed. The present study investigated the conditions that determine the transfer of logical recoding rules across tasks. Experiment 1 examined whether it occurs in a transfer paradigm, that is when the two tasks are performed separately, but provided little support for this possibility. Experiment 2 investigated the role of task-set readiness, using a mixed-task paradigm with a predictable trials sequence, which indicated that there is no transfer of task-defined rules across tasks even when they are highly active during the Simon task. Finally, Experiments 3 and 4 used a mixed-task paradigm, where trials of the two tasks were mixed randomly and unpredictably, and manipulated the amount of feature overlap between tasks. Results indicated that task similarity is a determining factor for transfer of task-defined rules to occur. Overall, the study provides evidence that transfer of logical recoding rules tends to occur across two tasks when tasks are unpredictably intermixed and use stimuli that are highly similar and confusable.

Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles.

PubMed

Mui, Barbara L; Tam, Ying K; Jayaraman, Muthusamy; Ansell, Steven M; Du, Xinyao; Tam, Yuen Yi C; Lin, Paulo Jc; Chen, Sam; Narayanannair, Jayaprakash K; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Akinc, Akin; Maier, Martin A; Cullis, Pieter; Madden, Thomas D; Hope, Michael J

2013-12-17

Lipid nanoparticles (LNPs) encapsulating short interfering RNAs that target hepatic genes are advancing through clinical trials, and early results indicate the excellent gene silencing observed in rodents and nonhuman primates also translates to humans. This success has motivated research to identify ways to further advance this delivery platform. Here, we characterize the polyethylene glycol lipid (PEG-lipid) components, which are required to control the self-assembly process during formation of lipid particles, but can negatively affect delivery to hepatocytes and hepatic gene silencing in vivo. The rate of transfer from LNPs to plasma lipoproteins in vivo is measured for three PEG-lipids with dialkyl chains 14, 16, and 18 carbons long. We show that 1.5 mol % PEG-lipid represents a threshold concentration at which the chain length exerts a minimal effect on hepatic gene silencing but can still modify LNPs pharmacokinetics and biodistribution. Increasing the concentration to 2.5 and 3.5 mol % substantially compromises hepatocyte gene knockdown for PEG-lipids with distearyl (C18) chains but has little impact for shorter dimyristyl (C14) chains. These data are discussed with respect to RNA delivery and the different rates at which the steric barrier disassociates from LNPs in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e139; doi:10.1038/mtna.2013.66; published online 17 December 2013.

Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate

PubMed Central

Boomer, Jeremy A.; Qualls, Marquita M.; Inerowicz, H. Dorota; Haynes, Robert H.; Patri, G.V. Srilaksmi; Kim, Jong-Mok; Thompson, David H.

2009-01-01

An acid-cleavable PEG lipid, 1′-(4′-cholesteryloxy-3′-butenyl)-ω-methoxy-polyethylene[112] glycolate (CVEP), has been developed that produces stable liposomes when dispersed as a minor component (0.5–5 mol%) in 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Cleavage of CVEP at mildly acidic pH’s results in dePEGylation of the latently fusogenic DOPE liposomes, thereby triggering the onset of contents release. This paper describes the synthesis of CVEP via a six step sequence starting from the readily available precursors 1,4-butanediol, cholesterol, and mPEG acid. The hydrolysis rates and release kinetics from CVEP:DOPE liposome dispersions as a function of CVEP loading, as well as the cryogenic transmission electron microscopy and pH-dependent monolayer properties of 9:91 CVEP:DOPE mixtures, also are reported. When folate-receptor positive KB cells were exposed to calcein-loaded 5:95 CVEP:DOPE liposomes containing 0.1 mol% folate-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene[76] glycolamide (folate-PEG-DSPE), efficient delivery of the calcein cargo to the cytoplasm of the cells was observed as determined by fluorescence microscopy and flow cytometry. Fluorescence resonance energy transfer analysis of lipid mixing in these cells was consistent with membrane-membrane fusion between the liposome and endosomal membranes. PMID:19072698

Development and validation of a surgical workload measure: the surgery task load index (SURG-TLX).

PubMed

Wilson, Mark R; Poolton, Jamie M; Malhotra, Neha; Ngo, Karen; Bright, Elizabeth; Masters, Rich S W

2011-09-01

The purpose of the present study was to develop and validate a multidimensional, surgery-specific workload measure (the SURG-TLX), and to determine its utility in providing diagnostic information about the impact of various sources of stress on the perceived demands of trained surgical operators. As a wide range of stressors have been identified for surgeons in the operating room, the current approach of considering stress as a unidimensional construct may not only limit the degree to which underlying mechanisms may be understood but also the degree to which training interventions may be successfully matched to particular sources of stress. The dimensions of the SURG-TLX were based on two current multidimensional workload measures and developed via focus group discussion. The six dimensions were defined as mental demands, physical demands, temporal demands, task complexity, situational stress, and distractions. Thirty novices were trained on the Fundamentals of Laparoscopic Surgery (FLS) peg transfer task and then completed the task under various conditions designed to manipulate the degree and source of stress experienced: task novelty, physical fatigue, time pressure, evaluation apprehension, multitasking, and distraction. The results were supportive of the discriminant sensitivity of the SURG-TLX to different sources of stress. The sub-factors loaded on the relevant stressors as hypothesized, although the evaluation pressure manipulation was not strong enough to cause a significant rise in situational stress. The present study provides support for the validity of the SURG-TLX instrument and also highlights the importance of considering how different stressors may load surgeons. Implications for categorizing the difficulty of certain procedures, the implementation of new technology in the operating room (man-machine interface issues), and the targeting of stress training strategies to the sources of demand are discussed. Modifications to the scale to enhance clinical utility are also suggested.

Laparoscopic skills training using a webcam trainer.

PubMed

Chung, Steve Y; Landsittel, Douglas; Chon, Chris H; Ng, Christopher S; Fuchs, Gerhard J

2005-01-01

Many sophisticated and expensive trainers have been developed to assist surgeons in learning basic laparoscopic skills. We developed an inexpensive trainer and evaluated its effectiveness. The webcam laparoscopic training device is composed of a webcam, cardboard box, desk lamp and home computer. This homemade trainer was evaluated against 2 commercially available systems, namely the video Pelvitrainer (Karl Storz Endoscopy, Culver City, California) and the dual mirror Simuview (Simulab Corp., Seattle, Washington). The Pelvitrainer consists of a fiberglass box, single lens optic laparoscope, fiberoptic light source, endoscopic camera and video monitor, while the Simuview trainer uses 2 offset, facing mirrors and an uncovered plastic box. A total of 42 participants without prior laparoscopic training were enrolled in the study and asked to execute 2 tasks, that is peg transfer and pattern cutting. Participants were randomly assigned to 6 groups with each group representing a different permutation of trainers to be used. The time required for participants to complete each task was recorded and differences in performance were calculated. Paired t tests, the Wilcoxon signed rank test and ANOVA were performed to analyze the statistical difference in performance times for all conditions. Statistical analyses of the 2 tasks showed no significant difference for the video and webcam trainers. However, the mirror trainer gave significantly higher outcome values for tasks 1 and 2 compared to the video (p = 0.01 and <0.01) and webcam (p = 0.04 and <0.01, respectively) methods. ANOVA indicated no overall difference for tasks 1 and 2 across the orderings (p = 0.36 and 0.99, respectively). However, by attempt 3 the time required to complete the skill tests decreased significantly for all 3 trainers (each p <0.01). Our homemade webcam system is comparable in function to the more elaborate video trainer but superior to the dual mirror trainer. For novice laparoscopists we believe that the webcam system is an inexpensive and effective laparoscopic training device. Furthermore, the webcam system also allows instant recording and review of techniques.

Transfer after Dual n-Back Training Depends on Striatal Activation Change.

PubMed

Salminen, Tiina; Kühn, Simone; Frensch, Peter A; Schubert, Torsten

2016-09-28

The dual n-back working memory (WM) training paradigm (comprising auditory and visual stimuli) has gained much attention since studies have shown widespread transfer effects. By including a multimodal dual-task component, the task is demanding to the human cognitive system. We investigated whether dual n-back training improves general cognitive resources or a task-specific WM updating process in participants. We expected: (1) widespread transfer effects and the recruitment of a common neuronal network by the training and the transfer tasks and (2) narrower transfer results and that a common activation network alone would not produce transfer, but instead an activation focus on the striatum, which is associated with WM updating processes. The training group showed transfer to an untrained dual-modality WM updating task, but not to single-task versions of the training or the transfer task. They also showed diminished neuronal overlap between the training and the transfer task from pretest to posttest and an increase in striatal activation in both tasks. Furthermore, we found an association between the striatal activation increase and behavioral improvement. The control groups showed no transfer and no change in the amount of activation overlap or in striatal activation from pretest to posttest. We conclude that, instead of improving general cognitive resources (which would have required a transfer effect to all transfer tasks and that a frontal activation overlap between the tasks produced transfer), dual n-back training improved a task-specific process: WM updating of stimuli from two modalities. The current study allows for a better understanding of the cognitive and neural effects of working memory (WM) training and transfer. It shows that dual n-back training mainly improves specific processes of WM updating, and this improvement leads to narrow transfer effects to tasks involving the same processes. On a neuronal level this is accompanied by increased neural activation in the striatum that is related to WM updating. The current findings challenge the view that dual n-back training provokes a general boosting of the WM system and of its neural underpinnings located in frontoparietal brain regions. Instead, the findings imply the relevance of task-specific brain regions which are involved in important cognitive processes during training and transfer tasks. Copyright © 2016 the authors 0270-6474/16/3610198-16$15.00/0.

Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): in vitro and in vivo studies.

PubMed

Kim, Eun-Mi; Jeong, Hwan-Jeong; Park, In-Kyu; Cho, Chong-Su; Moon, Hyung-Bae; Yu, Dae-Yeul; Bom, Hee-Seung; Sohn, Myung-Hee; Oh, In-Joon

2005-11-28

The asialoglycoprotein receptor (ASGP-R) on the hepatocyte membrane is a specific targeting marker for gene and drug delivery. Polyethylenimine (PEI) is a polycationic nonviral vector that is used for gene transfer. We have synthesized galactosylated polyethylenimine-graft-poly(ethylene glycol) (GPP) for performing gene delivery to the hepatocytes. The present study reports on the in vitro and in vivo data that was achieved in hepatoma bearing transgenic mice. The cytotoxicity was decreased with the increasing PEG content. The particle size of the complex was increased with the increasing PEG at an N/P ratio of 3.0, while the zeta potentials were decreased. The (99m)Tc labeled complexes were transfected into HepG2 and HeLa cells, while the GFP reporter genes were mainly expressed in the HepG2 cells. The in vivo data was achieved in ALB/c-Ha-ras transgenic mice. (99m)Tc labeled GPP(50)/DNA was injected into the mice via the tail vein, and the gamma images were acquired at 5, 15 and 30 min. The (99m)Tc labeled complexes were mainly localized in the heart and liver, and they were excreted through the kidneys. The GFP gene was mainly expressed in the proliferating cells at the tumor periphery. This result was confirmed by PCNA staining. The GPP(50)/DNA complexes were bound to ASGP-R of the proliferating hepatocytes in vitro and in vivo. The present results demonstrate the feasibility of nonviral gene transfer using galactosylated PEI-PEG in vivo.

Force-reflection and shared compliant control in operating telemanipulators with time delay

NASA Technical Reports Server (NTRS)

Kim, Won S.; Hannaford, Blake; Bejczy, Antal K.

1992-01-01

The performance of an advanced telemanipulation system in the presence of a wide range of time delays between a master control station and a slave robot is quantified. The contemplated applications include multiple satellite links to LEO, geosynchronous operation, spacecraft local area networks, and general-purpose computer-based short-distance designs. The results of high-precision peg-in-hole tasks performed by six test operators indicate that task performance decreased linearly with introduced time delays for both kinesthetic force feedback (KFF) and shared compliant control (SCC). The rate of this decrease was substantially improved with SCC compared to KFF. Task performance at delays above 1 s was not possible using KFF. SCC enabled task performance for such delays, which are realistic values for ground-controlled remote manipulation of telerobots in space.

Unstable Memories Create a High-Level Representation that Enables Learning Transfer.

PubMed

Mosha, Neechi; Robertson, Edwin M

2016-01-11

A memory is unstable, making it susceptible to interference and disruption, after its acquisition [1-4]. The function or possible benefit of a memory being unstable at its acquisition is not well understood. Potentially, instability may be critical for the communication between recently acquired memories, which would allow learning in one task to be transferred to the other subsequent task [1, 5]. Learning may be transferred between any memories that are unstable, even between different types of memory. Here, we test the link between a memory being unstable and the transfer of learning to a different type of memory task. We measured how learning in one task transferred to and thus improved learning in a subsequent task. There was transfer from a motor skill to a word list task and, vice versa, from a word list to a motor skill task. What was transferred was a high-level relationship between elements, rather than knowledge of the individual elements themselves. Memory instability was correlated with subsequent transfer, suggesting that transfer was related to the instability of the memory. Using different methods, we stabilized the initial memory, preventing it from being susceptible to interference, and found that these methods consistently prevented transfer to the subsequent memory task. This suggests that the transfer of learning across diverse tasks is due to a high-level representation that can only be formed when a memory is unstable. Our work has identified an important function of memory instability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Context transfer in reinforcement learning using action-value functions.

PubMed

Mousavi, Amin; Nadjar Araabi, Babak; Nili Ahmadabadi, Majid

2014-01-01

This paper discusses the notion of context transfer in reinforcement learning tasks. Context transfer, as defined in this paper, implies knowledge transfer between source and target tasks that share the same environment dynamics and reward function but have different states or action spaces. In other words, the agents learn the same task while using different sensors and actuators. This requires the existence of an underlying common Markov decision process (MDP) to which all the agents' MDPs can be mapped. This is formulated in terms of the notion of MDP homomorphism. The learning framework is Q-learning. To transfer the knowledge between these tasks, the feature space is used as a translator and is expressed as a partial mapping between the state-action spaces of different tasks. The Q-values learned during the learning process of the source tasks are mapped to the sets of Q-values for the target task. These transferred Q-values are merged together and used to initialize the learning process of the target task. An interval-based approach is used to represent and merge the knowledge of the source tasks. Empirical results show that the transferred initialization can be beneficial to the learning process of the target task.

Context Transfer in Reinforcement Learning Using Action-Value Functions

PubMed Central

Mousavi, Amin; Nadjar Araabi, Babak; Nili Ahmadabadi, Majid

2014-01-01

This paper discusses the notion of context transfer in reinforcement learning tasks. Context transfer, as defined in this paper, implies knowledge transfer between source and target tasks that share the same environment dynamics and reward function but have different states or action spaces. In other words, the agents learn the same task while using different sensors and actuators. This requires the existence of an underlying common Markov decision process (MDP) to which all the agents' MDPs can be mapped. This is formulated in terms of the notion of MDP homomorphism. The learning framework is Q-learning. To transfer the knowledge between these tasks, the feature space is used as a translator and is expressed as a partial mapping between the state-action spaces of different tasks. The Q-values learned during the learning process of the source tasks are mapped to the sets of Q-values for the target task. These transferred Q-values are merged together and used to initialize the learning process of the target task. An interval-based approach is used to represent and merge the knowledge of the source tasks. Empirical results show that the transferred initialization can be beneficial to the learning process of the target task. PMID:25610457

Transfer of perceptual learning between different visual tasks

PubMed Central

McGovern, David P.; Webb, Ben S.; Peirce, Jonathan W.

2012-01-01

Practice in most sensory tasks substantially improves perceptual performance. A hallmark of this ‘perceptual learning' is its specificity for the basic attributes of the trained stimulus and task. Recent studies have challenged the specificity of learned improvements, although transfer between substantially different tasks has yet to be demonstrated. Here, we measure the degree of transfer between three distinct perceptual tasks. Participants trained on an orientation discrimination, a curvature discrimination, or a ‘global form' task, all using stimuli comprised of multiple oriented elements. Before and after training they were tested on all three and a contrast discrimination control task. A clear transfer of learning was observed, in a pattern predicted by the relative complexity of the stimuli in the training and test tasks. Our results suggest that sensory improvements derived from perceptual learning can transfer between very different visual tasks. PMID:23048211

Transfer of perceptual learning between different visual tasks.

PubMed

McGovern, David P; Webb, Ben S; Peirce, Jonathan W

2012-10-09

Practice in most sensory tasks substantially improves perceptual performance. A hallmark of this 'perceptual learning' is its specificity for the basic attributes of the trained stimulus and task. Recent studies have challenged the specificity of learned improvements, although transfer between substantially different tasks has yet to be demonstrated. Here, we measure the degree of transfer between three distinct perceptual tasks. Participants trained on an orientation discrimination, a curvature discrimination, or a 'global form' task, all using stimuli comprised of multiple oriented elements. Before and after training they were tested on all three and a contrast discrimination control task. A clear transfer of learning was observed, in a pattern predicted by the relative complexity of the stimuli in the training and test tasks. Our results suggest that sensory improvements derived from perceptual learning can transfer between very different visual tasks.

Specificity and transfer effects in time production skill: examining the role of attention.

PubMed

Wohldmann, Erica L; Healy, Alice F; Bourne, Lyle E

2012-05-01

Two experiments examined transfer of a prospective, time production skill under conditions involving changes in concurrent task requirements. Positive transfer of the time production skill might be expected only when the attentional demands of the concurrent task were held constant from training to test. However, some positive transfer was found even when the concurrent task at retraining was made either easier or more difficult than the concurrent task learned during training. The amount and direction of transfer depended more on the pacing of the stimuli in the secondary task than on the difficulty of the secondary task, even though difficulty affects attentional demands more. These findings are consistent with the procedural reinstatement principle of skill learning, by which transfer from one task to another depends on an overlap in procedures required by the two skills.

Upper limb assessment using a Virtual Peg Insertion Test.

PubMed

Fluet, Marie-Christine; Lambercy, Olivier; Gassert, Roger

2011-01-01

This paper presents the initial evaluation of a Virtual Peg Insertion Test developed to assess sensorimotor functions of arm and hand using an instrumented tool, virtual reality and haptic feedback. Nine performance parameters derived from kinematic and kinetic data were selected and compared between two groups of healthy subjects performing the task with the dominant and non-dominant hand, as well as with a group of chronic stroke subjects suffering from different levels of upper limb impairment. Results showed significantly smaller grasping forces applied by the stroke subjects compared to the healthy subjects. The grasping force profiles suggest a poor coordination between position and grasping for the stroke subjects, and the collision forces with the virtual board were found to be indicative of sensory deficits. These preliminary results suggest that the analyzed parameters could be valid indicators of impairment. © 2011 IEEE

Modifications of adenovirus hexon allow for either hepatocyte detargeting or targeting with potential evasion from Kupffer cells.

PubMed

Prill, Jan-Michael; Espenlaub, Sigrid; Samen, Ulrike; Engler, Tatjana; Schmidt, Erika; Vetrini, Francesco; Rosewell, Amanda; Grove, Nathan; Palmer, Donna; Ng, Philip; Kochanek, Stefan; Kreppel, Florian

2011-01-01

In vivo gene transfer with adenovirus vectors would significantly benefit from a tight control of the adenovirus-inherent liver tropism. For efficient hepatocyte transduction, adenovirus vectors need to evade from Kupffer cell scavenging while delivery to peripheral tissues or tumors could be improved if both scavenging by Kupffer cells and uptake by hepatocytes were blocked. Here, we provide evidence that a single point mutation in the hexon capsomere designed to enable defined chemical capsid modifications may permit both detargeting from and targeting to hepatocytes with evasion from Kupffer cell scavenging. Vector particles modified with small polyethylene glycol (PEG) moieties specifically on hexon exhibited decreased transduction of hepatocytes by shielding from blood coagulation factor binding. Vector particles modified with transferrin or, surprisingly, 5,000 Da PEG or dextran increased hepatocyte transduction up to 18-fold independent of the presence of Kupffer cells. We further show that our strategy can be used to target high-capacity adenovirus vectors to hepatocytes emphasizing the potential for therapeutic liver-directed gene transfer. Our approach may lead to a detailed understanding of the interactions between adenovirus vectors and Kupffer cells, one of the most important barriers for adenovirus-mediated gene delivery.

Multifunctional PEG-carboxylate copolymer coated superparamagnetic iron oxide nanoparticles for biomedical application

NASA Astrophysics Data System (ADS)

Illés, Erzsébet; Szekeres, Márta; Tóth, Ildikó Y.; Szabó, Ákos; Iván, Béla; Turcu, Rodica; Vékás, Ladislau; Zupkó, István; Jaics, György; Tombácz, Etelka

2018-04-01

Biocompatible magnetite nanoparticles (MNPs) were prepared by post-coating the magnetic nanocores with a synthetic polymer designed specifically to shield the particles from non-specific interaction with cells. Poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomers and acrylic acid (AA) small molecular monomers were chemically coupled by quasi-living atom transfer radical polymerization (ATRP) to a comb-like copolymer, P(PEGMA-co-AA) designated here as P(PEGMA-AA). The polymer contains pendant carboxylate moieties near the backbone and PEG side chains. It is able to bind spontaneously to MNPs; stabilize the particles electrostatically via the carboxylate moieties and sterically via the PEG moieties; provide high protein repellency via the structured PEG layer; and anchor bioactive proteins via peptide bond formation with the free carboxylate groups. The presence of the P(PEGMA-AA) coating was verified in XPS experiments. The electrosteric (i.e., combined electrostatic and steric) stabilization is efficient down to pH 4 (at 10 mM ionic strength). Static magnetization and AC susceptibility measurements showed that the P(PEGMA-AA)@MNPs are superparamagnetic with a saturation magnetization value of 55 emu/g and that both single core nanoparticles and multicore structures are present in the samples. The multicore components make our product well suited for magnetic hyperthermia applications (SAR values up to 17.44 W/g). In vitro biocompatibility, cell internalization, and magnetic hyperthermia studies demonstrate the excellent theranostic potential of our product.

Unique regulatory properties of the UDP-glucose:. beta. -1,4-glucan synthetase of Acetobacter xylinum. [Acetobacter xylinum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benziman, M.; Aloni, Y.; Delmer, D.P.

1983-01-01

Conditions have been found for an extremely efficient transfer of glucose from UDP-glucose to a cellulosic ..beta..-1,4-glucan product, using enzyme preparations derived from cells of Acetobacter xylinum. Membrane fractions obtained by rupturing cells in the presence of 20% (w/v) polyethylene glycol-4000 (PEG-4000) exhibited UDP-glucose:..beta..-1,4-glucan synthetase activity 3- to 10-fold higher than those previously reported. Enzyme prepared in this fashion also shows a further marked activation by GTP. The activation (apparent K/sub alpha/ = 35 ..mu..M) is quite specific for GTP. A variety of other nucleotides and nucleotide derivatives had no effect on activity. Guanosine-5'-(lambda-thio)triphosphate, an analog of GTP, is evenmore » more efficient than GTP (K/sub alpha/ = 17 ..mu..M). Enzyme prepared in the absence of PEG-4000 does not respond to GTP because it lacks a protein factor essential for GTP activation. PEG-4000 promotes the interaction of the protein factor with the enzyme. The factor itself is devoid of synthetase activity and does not stimulate activity of the enzyme in the absence of GTP. Under optimal conditions, in the presence of GTP, factor, and PEG-4000, initial rates of enzyme activity that are 200 times higher than those previously reported can be achieved. Such rates exceed 40% of the in vivo rate of cellulose synthesis from glucose. 26 references, 3 figures, 3 tables.« less

An RGD-Modified MRI-Visible Polymeric Vector for Targeted siRNA Delivery to Hepatocellular Carcinoma in Nude Mice

PubMed Central

Shen, Min; Zhu, Kangshun; Cheng, Du; Liu, Zhihao; Shan, Hong

2013-01-01

RNA interference (RNAi) has significant therapeutic promise for the genetic treatment of hepatocellular carcinoma (HCC). Targeted vectors are able to deliver small interfering RNA (siRNA) into HCC cells with high transfection efficiency and stability. The tripeptide arginine glycine aspartic acid (RGD)-modified non-viral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (RGD-PEG-g-PEI-SPION), was constructed as a magnetic resonance imaging (MRI)-visible nanocarrier for the delivery of Survivin siRNA targeting the human HCC cell line Bel-7402. The biophysical characterization of the RGD-PEG-g-PEI-SPION was performed. The RGD-modified complexes exhibited a higher transfection efficiency in transferring Survivin siRNA into Bel-7402 cells compared with a non-targeted delivery system, which resulted in more significant gene suppression at both the Survivin mRNA and protein expression levels. Then, the level of caspase-3 activation was significantly elevated, and a remarkable level of tumor cell apoptosis was induced. As a result, the tumor growth in the nude mice Bel-7402 hepatoma model was significantly inhibited. The targeting ability of the RGD-PEG-g-PEI-SPION was successfully imaged by MRI scans performed in vitro and in vivo. Our results strongly indicated that the RGD-PEG-g-PEI-SPION can potentially be used as a targeted non-viral vector for altering gene expression in the treatment of hepatocellular carcinoma and for detecting the tumor in vivo as an effective MRI probe. PMID:23922634

Impact of simulated three-dimensional perception on precision of depth judgements, technical performance and perceived workload in laparoscopy.

PubMed

Sakata, S; Grove, P M; Hill, A; Watson, M O; Stevenson, A R L

2017-07-01

This study compared precision of depth judgements, technical performance and workload using two-dimensional (2D) and three-dimensional (3D) laparoscopic displays across different viewing distances. It also compared the accuracy of 3D displays with natural viewing, along with the relationship between stereoacuity and 3D laparoscopic performance. A counterbalanced within-subjects design with random assignment to testing sequences was used. The system could display 2D or 3D images with the same set-up. A Howard-Dolman apparatus assessed precision of depth judgements, and three laparoscopic tasks (peg transfer, navigation in space and suturing) assessed performance (time to completion). Participants completed tasks in all combinations of two viewing modes (2D, 3D) and two viewing distances (1 m, 3 m). Other measures administered included the National Aeronautics and Space Administration Task Load Index (perceived workload) and the Randot ® Stereotest (stereoacuity). Depth judgements were 6·2 times as precise at 1 m and 3·0 times as precise at 3 m using 3D versus 2D displays (P < 0·001). Participants performed all laparoscopic tasks faster in 3D at both 1 and 3 m (P < 0.001), with mean completion times up to 64 per cent shorter for 3D versus 2D displays. Workload was lower for 3D displays (up to 34 per cent) than for 2D displays at both viewing distances (P < 0·001). Greater viewing distance inhibited performance for two laparoscopic tasks, and increased perceived workload for all three (P < 0·001). Higher stereoacuity was associated with shorter completion times for the navigating in space task performed in 3D at 1 m (r = - 0·40, P = 0·001). 3D displays offer large improvements over 2D displays in precision of depth judgements, technical performance and perceived workload. © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Inhibitory Control in Preschool Predicts Early Math Skills in First Grade: Evidence from an Ethnically Diverse Sample

ERIC Educational Resources Information Center

Ng, Florrie Fei-Yin; Tamis-LeMonda, Catherine; Yoshikawa, Hirokazu; Sze, Irene Nga-Lam

2015-01-01

Preschoolers' inhibitory control and early math skills were concurrently and longitudinally examined in 255 Chinese, African American, Dominican, and Mexican 4-year-olds in the United States. Inhibitory control at age 4, assessed with a peg-tapping task, was associated with early math skills at age 4 and predicted growth in such skills from age 4…

Interdisciplinary rehabilitation for a patient with incomplete cervical spinal cord injury and multimorbidity: A case report.

PubMed

Vining, Robert D; Gosselin, Donna M; Thurmond, Jeb; Case, Kimberlee; Bruch, Frederick R

2017-08-01

This report describes interdisciplinary rehabilitation for a 51-year-old male recovering from incomplete cervical spinal cord injury (SCI) and multiple comorbidities following an automobile accident. The patient was admitted to a rehabilitation specialty hospital approximately 2 months post SCI and 2 separate surgical fusion procedures (C3-C6). Clinical presentation at the rehabilitation hospital included moderate to severe motor strength loss in both upper and lower extremities, a percutaneous endoscopic gastronomy tube (PEG), dysphagia, bowel/bladder incontinence, dependence on a mechanical lift and tilting wheelchair due to severe orthostatic hypotension, and pre-existing shoulder pain from bilateral joint degeneration. The interdisciplinary team formally coordinated rehabilitative care from multiple disciplines. Internal medicine managed medications, determined PEG removal, monitored co-morbid conditions, and overall progress. Chiropractic care focused on alleviating shoulder and thoracic pain and improving spinal and extremity mobility. Physical therapy addressed upright tolerance, transfer, gait, and strength training. Occupational therapy focused on hand coordination and feeding/dressing activities. Psychology assisted with coping strategies. Nursing ensured medication adherence, nutrient intake, wound prevention, and incontinence management, whereas physiatry addressed abnormal muscle tone. Eleven months post-admission the patient's progress allowed discharge to a long-term care facility. At this time he was without dysphagia or need for a PEG. Orthostatic hypotension and bilateral shoulder pain symptoms were also resolved while bowel/bladder incontinence and upper and lower extremity motor strength loss remained. He was largely independent in transferring from bed to wheelchair and in upper body dressing. Lower body dressing/bathing required maximal assistance. Gait with a 2-wheeled walker was possible up to 150 feet with verbal cues and occasional stabilizing assistance. Several specialties functioning within an interdisciplinary team fulfilled complementary roles to support rehabilitation for a patient with SCI.

EGFR-targeted nonviral NIS gene transfer for bioimaging and therapy of disseminated colon cancer metastases

PubMed Central

Urnauer, Sarah; Müller, Andrea M.; Schug, Christina; Schmohl, Kathrin A.; Tutter, Mariella; Schwenk, Nathalie; Rödl, Wolfgang; Morys, Stephan; Ingrisch, Michael; Bertram, Jens; Bartenstein, Peter; Clevert, Dirk-André; Wagner, Ernst; Spitzweg, Christine

2017-01-01

Liver metastases present a serious problem in the therapy of advanced colorectal cancer (CRC), as more than 20% of patients have distant metastases at the time of diagnosis with less than 5% being cured. Consequently, new therapeutic approaches are of major need together with high-resolution imaging methods that allow highly specific detection of small metastases. The unique combination of reporter and therapy gene function of the sodium iodide symporter (NIS) may represent a promising theranostic strategy for CRC liver metastases allowing non-invasive imaging of functional NIS expression and therapeutic application of 131I. For targeted NIS gene transfer polymers containing linear polyethylenimine (LPEI), polyethylene glycol (PEG) and the epidermal growth factor receptor (EGFR)-specific ligand GE11 were complexed with human NIS DNA (LPEI-PEG-GE11/NIS). Tumor specificity and transduction efficiency were examined in high EGFR-expressing LS174T metastases by non-invasive imaging using 18F-tetrafluoroborate (18F-TFB) as novel NIS PET tracer. Mice that were injected with LPEI-PEG-GE11/NIS 48 h before 18F-TFB application showed high tumoral levels (4.8±0.6% of injected dose) of NIS-mediated radionuclide uptake in comparison to low levels detected in mice that received untargeted control polyplexes. Three cycles of intravenous injection of EGFR-targeted NIS polyplexes followed by therapeutic application of 55.5 MBq 131I resulted in marked delay in metastases spread, which was associated with improved animal survival. In conclusion, these preclinical data confirm the enormous potential of EGFR-targeted synthetic polymers for systemic NIS gene delivery in an advanced multifocal CRC liver metastases model and open the exciting prospect of NIS-mediated radionuclide therapy in metastatic disease. PMID:29190908

PEGylation of Concanavalin A to decrease nonspecific interactions in a fluorescent glucose sensor

NASA Astrophysics Data System (ADS)

Abraham, Alexander A.; Cummins, Brian M.; Locke, Andrea K.; Grunlan, Melissa A.; Coté, Gerard L.

2014-02-01

The ability of people with diabetes to both monitor and regulate blood sugar levels is limited by the conventional "finger-prick" test that provides intermittent, single point measurements. Toward the development of a continuous glucose monitoring (CGM) system, the lectin, Concanavalin A (ConA), has been utilized as a component in a Förster resonance energy transfer (FRET), competitive glucose binding assay. Recently, to avoid reversibility problems associated with ConA aggregation, a suitable competing ligand labeled with 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt (APTS) has been engineered. However, its ability to function as part of a glucose sensing assay is compromised due to the negative charge (at physiological pH) of native ConA that gives rise to non-specific binding with other ConA groups as well as with electrostatically charged assay-delivery carriers. To minimize these undesirable interactions, we have conjugated ConA with monomethoxy-poly(ethylene glycol) (mPEG) (i.e. "PEGylation"). In this preliminary research, fluorescently-labeled ConA was successfully PEGylated with mPEG-Nhydroxylsuccinimide( succinimidyl carbonate) (mPEG-NHS(SC)). The FRET response of APTS-labeled competing ligand (donor) conveyed an increase in the fluorescence intensity with increasing glucose concentrations.

[Indications for percutaneous endoscopic gastrostomy in patients with disorders of the nervous system].

PubMed

Ehler, E; Geier, P; Dostál, V; Novotná, A; Vyhnálek, P; Hájek, J; Sákra, L

2002-05-01

Percutaneous endoscopic gastrostomy (PEG) is an efficient endoscopic method that ensures enteral nutrition for a longer period of time in patients who cannot take food per os. This method is also indicated in patients suffering from disorders of the central or peripheral nervous system which developed suddenly, such as a stroke or craniocerebral injuries, or gradually, such as amyotrophic lateral sclerosis (ALS), dementia, and multiple sclerosis. It has become common practice in the cooperation between neurologists and a gastroenterologists to use PEG in patients hospitalized in a neurological ward with encephalomalacy and haemorrhage, or craniocerebral injuries (after the patient recovers from the acute stage of the disease and is transferred to a neurological ICU), as well as in patients with ALS in a progressive stage. We gradually extend the indications of PEG for other patients with neurological disorders such as patients suffering from dementia, progressive multiple sclerosis, Parkinson's disease, and progressive polyneuropathy. Of 62 patients hospitalized in a neurological ward during a period of 4.5 years, 56 patients suffered from sudden disorders of the nervous system (strokes and craniocerebral injuries) and 6 patients had gradually progressing neurological diseases (ALS, multiple sclerosis, Parkinson's disease, dementia, and polyneuropathy).

Fabrication and biological imaging of polyhedral oligomeric silsesquioxane cross-linked fluorescent polymeric nanoparticles with aggregation-induced emission feature

NASA Astrophysics Data System (ADS)

Mao, Liucheng; Liu, Meiying; Xu, Dazhuang; Wan, Qing; Huang, Qiang; Jiang, Ruming; Shi, Yingge; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-11-01

Aggregation-induced emission (AIE) dyes based fluorescent polymeric nanoparticles (FNPs) have been intensively explored for biomedical applications. However, many of these AIE-active FNPs are relied on the self-assembly of amphiphilic copolymers, which are not stable in diluted solution. Therefore, the introduction of cross-linkages into these micelles has demonstrated to be an efficient route to overcome this stability problem and endow ultra-low critical micelle concentrations (CMC) of these AIE-active FNPs. In this work, we reported the fabrication of cross-linked AIE-active FNPs through controllable reversible addition fragmentation chain transfer polymerization by using commercially available octavinyl-T8-silsesquioxane (8-vinyl POSS) as the cross-linkage for the first time. The resultant cross-linked amphiphilic copolymers (named as PEG-POSS-PhE) are prone to self-assemble into stable core-shell nanoparticles with well water dispersity, strong red fluorescence and low CMC (0.0069 mg mL-1) in aqueous solution. More importantly, PEG-POSS-PhE FNPs possess some other properties such as high water dispersity, uniform morphology and small size, excellent biocompatibility and cellular internalization, providing great potential of PEG-POSS-PhE FNPs for biological imaging application.

Gestures make memories, but what kind? Patients with impaired procedural memory display disruptions in gesture production and comprehension

PubMed Central

Klooster, Nathaniel B.; Cook, Susan W.; Uc, Ergun Y.; Duff, Melissa C.

2015-01-01

Hand gesture, a ubiquitous feature of human interaction, facilitates communication. Gesture also facilitates new learning, benefiting speakers and listeners alike. Thus, gestures must impact cognition beyond simply supporting the expression of already-formed ideas. However, the cognitive and neural mechanisms supporting the effects of gesture on learning and memory are largely unknown. We hypothesized that gesture's ability to drive new learning is supported by procedural memory and that procedural memory deficits will disrupt gesture production and comprehension. We tested this proposal in patients with intact declarative memory, but impaired procedural memory as a consequence of Parkinson's disease (PD), and healthy comparison participants with intact declarative and procedural memory. In separate experiments, we manipulated the gestures participants saw and produced in a Tower of Hanoi (TOH) paradigm. In the first experiment, participants solved the task either on a physical board, requiring high arching movements to manipulate the discs from peg to peg, or on a computer, requiring only flat, sideways movements of the mouse. When explaining the task, healthy participants with intact procedural memory displayed evidence of their previous experience in their gestures, producing higher, more arching hand gestures after solving on a physical board, and smaller, flatter gestures after solving on a computer. In the second experiment, healthy participants who saw high arching hand gestures in an explanation prior to solving the task subsequently moved the mouse with significantly higher curvature than those who saw smaller, flatter gestures prior to solving the task. These patterns were absent in both gesture production and comprehension experiments in patients with procedural memory impairment. These findings suggest that the procedural memory system supports the ability of gesture to drive new learning. PMID:25628556

Policy Transfer via Markov Logic Networks

NASA Astrophysics Data System (ADS)

Torrey, Lisa; Shavlik, Jude

We propose using a statistical-relational model, the Markov Logic Network, for knowledge transfer in reinforcement learning. Our goal is to extract relational knowledge from a source task and use it to speed up learning in a related target task. We show that Markov Logic Networks are effective models for capturing both source-task Q-functions and source-task policies. We apply them via demonstration, which involves using them for decision making in an initial stage of the target task before continuing to learn. Through experiments in the RoboCup simulated-soccer domain, we show that transfer via Markov Logic Networks can significantly improve early performance in complex tasks, and that transferring policies is more effective than transferring Q-functions.

Effects of Selected Task Performance Criteria at Initiating Adaptive Task Real locations

NASA Technical Reports Server (NTRS)

Montgomery, Demaris A.

2001-01-01

In the current report various performance assessment methods used to initiate mode transfers between manual control and automation for adaptive task reallocation were tested. Participants monitored two secondary tasks for critical events while actively controlling a process in a fictional system. One of the secondary monitoring tasks could be automated whenever operators' performance was below acceptable levels. Automation of the secondary task and transfer of the secondary task back to manual control were either human- or machine-initiated. Human-initiated transfers were based on the operator's assessment of the current task demands while machine-initiated transfers were based on the operators' performance. Different performance assessment methods were tested in two separate experiments.

POLYELECTROLYTE MULTILAYER STAMPING IN AQUEOUS PHASE AND NON-CONTACT MODE

PubMed Central

Mehrotra, Sumit; Lee, Ilsoon; Liu, Chun; Chan, Christina

2011-01-01

Polyelectrolyte multilayer (PEM) transfer printing has been previously achieved by stamping under dry conditions. Here, we show for the first time, that PEM can be transferred from a stamp to the base substrate under aqueous conditions whereby the two surfaces are in a non-contact mode. Degradable multilayers of (PAA/PEG)10.5 followed by non-degradable multilayers of (PDAC/SPS)80.5 were fabricated under acidic pH conditions on either PDMS or glass (stamp), and subsequently transferred over top of another multilayer prepared on a different substrate (base substrate), with a spacing of ~ 200 μm between the stamping surface and the base substrate. This multilayer transfer was performed under physiological pH conditions. This process is referred to herein as non-contact, aqueous-phase multilayer (NAM) transfer. NAM transfer can be useful for applications such as fabricating three-dimensional (3-D) cellular scaffolds. We attempted to create a 3-D cellular scaffold using NAM transfer, and characterized the scaffolds with conventional and fluorescence microscopy. PMID:21860540

Specific transfer effects following variable priority dual-task training in older adults.

PubMed

Lussier, Maxime; Bugaiska, Aurélia; Bherer, Louis

2017-01-01

Past divided attention training studies in older adults have suggested that variable priority training (VPT) tends to show larger improvement than fixed priority training (FPT). However, it remains unclear whether VPT leads to larger transfer effects. In this study, eighty-three older adults aged between 55 and 65 received five 1-hour sessions of VPT, FPT or of an active placebo. VPT and FPT subjects trained on a complex dual-task condition with variable stimulus timings in order to promote more flexible and self-guided strategies with regard to attentional priority devoted to the concurrent tasks. Real-time individualized feedback was provided to encourage improvement. The active placebo group attended computer classes. Near and far modality transfer tasks were used to assess the generalization of transfer effects. Results showed that VPT induced significantly larger transfer effects than FPT on a near modality transfer task. Evidence for larger transfer effects in VPT than FPT on a far modality transfer task was also observed. Furthermore, the superiority of VPT on FPT in transfer effects was specific to the ability to coordinate two concurrent tasks. Results of this study help better understand the benefits of VPT attentional training on transfer effects, which is an essential outcome for cognitive training effectiveness and relevancy.

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro.

PubMed

Xiang, Guang-Hua; Hong, Guo-Bin; Wang, Yong; Cheng, Du; Zhou, Jing-Xing; Shuai, Xin-Tao

2013-01-01

To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms. PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined. Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA-DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells. The PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic effect against human hepatocellular carcinoma HepG2 cells.

An acoustofluidic micromixer via bubble inception and cavitation from microchannel sidewalls.

PubMed

Ozcelik, Adem; Ahmed, Daniel; Xie, Yuliang; Nama, Nitesh; Qu, Zhiguo; Nawaz, Ahmad Ahsan; Huang, Tony Jun

2014-05-20

During the deep reactive ion etching process, the sidewalls of a silicon mold feature rough wavy structures, which can be transferred onto a polydimethylsiloxane (PDMS) microchannel through the soft lithography technique. In this article, we utilized the wavy structures of PDMS microchannel sidewalls to initiate and cavitate bubbles in the presence of acoustic waves. Through bubble cavitation, this acoustofluidic approach demonstrates fast, effective mixing in microfluidics. We characterized its performance by using viscous fluids such as poly(ethylene glycol) (PEG). When two PEG solutions with a resultant viscosity 54.9 times higher than that of water were used, the mixing efficiency was found to be 0.92, indicating excellent, homogeneous mixing. The acoustofluidic micromixer presented here has the advantages of simple fabrication, easy integration, and capability to mix high-viscosity fluids (Reynolds number: ~0.01) in less than 100 ms.

Dissociation of first- and second-order motion systems by perceptual learning

PubMed Central

Chubb, Charles

2013-01-01

Previous studies investigating transfer of perceptual learning between luminance-defined (LD) motion and texture-contrast-defined (CD) motion tasks have found little or no transfer from LD to CD motion tasks but nearly perfect transfer from CD to LD motion tasks. Here, we introduce a paradigm that yields a clean double dissociation: LD training yields no transfer to the CD task, but more interestingly, CD training yields no transfer to the LD task. Participants were trained in two variants of a global motion task. In one (LD) variant, motion was defined by tokens that differed from the background in mean luminance. In the other (CD) variant, motion was defined by tokens that had mean luminance equal to the background but differed from the background in texture contrast. The task was to judge whether the signal tokens were moving to the right or to the left. Task difficulty was varied by manipulating the proportion of tokens that moved coherently across the four frames of the stimulus display. Performance in each of the LD and CD variants of the task was measured as training proceeded. In each task, training produced substantial improvement in performance in the trained task; however, in neither case did this improvement show any significant transfer to the nontrained task. PMID:22477056

Nominal and functional task difficulty in skill acquisition: Effects on performance in two tests of transfer.

PubMed

Sanli, Elizabeth A; Lee, Timothy D

2015-06-01

The influence of nominal and functional task difficulty during the acquisition of a motor skill was examined in two tests of transfer of learning. The task involved a ballistic, target-directed, finger action. Nominal task difficulty was defined as the distance of the target from the home position. Functional task difficulty was created by manipulating the progression of target distances during practice. Based on the challenge point framework (Guadagnoli & Lee, 2004), we predicted that practice with a set of targets farther away from the performer would benefit from less functional task difficulty, while practice with a closer set of targets would benefit from more functional task difficulty. In single-task transfer tests, learners who practiced using the high nominal task difficulty targets benefitted in terms of persistence of performance over time. In dual-task transfer tests, groups with an intermediate combined (nominal and functional) task difficulty performed with greater persistence over time on tests of transfer than those who practiced with the highest or lowest combined difficulty. Together these findings suggest that the influences of nominal and functional task difficulty during acquisition are weighted differentially depending upon the transfer test context. The challenge point framework does not accurately capture this complex relationship in its current form. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-task transfer learning deep convolutional neural network: application to computer-aided diagnosis of breast cancer on mammograms

NASA Astrophysics Data System (ADS)

Samala, Ravi K.; Chan, Heang-Ping; Hadjiiski, Lubomir M.; Helvie, Mark A.; Cha, Kenny H.; Richter, Caleb D.

2017-12-01

Transfer learning in deep convolutional neural networks (DCNNs) is an important step in its application to medical imaging tasks. We propose a multi-task transfer learning DCNN with the aim of translating the ‘knowledge’ learned from non-medical images to medical diagnostic tasks through supervised training and increasing the generalization capabilities of DCNNs by simultaneously learning auxiliary tasks. We studied this approach in an important application: classification of malignant and benign breast masses. With Institutional Review Board (IRB) approval, digitized screen-film mammograms (SFMs) and digital mammograms (DMs) were collected from our patient files and additional SFMs were obtained from the Digital Database for Screening Mammography. The data set consisted of 2242 views with 2454 masses (1057 malignant, 1397 benign). In single-task transfer learning, the DCNN was trained and tested on SFMs. In multi-task transfer learning, SFMs and DMs were used to train the DCNN, which was then tested on SFMs. N-fold cross-validation with the training set was used for training and parameter optimization. On the independent test set, the multi-task transfer learning DCNN was found to have significantly (p  =  0.007) higher performance compared to the single-task transfer learning DCNN. This study demonstrates that multi-task transfer learning may be an effective approach for training DCNN in medical imaging applications when training samples from a single modality are limited.

Are training and transfer effects of working memory updating training modulated by achievement motivation?

PubMed

Zhao, Xin; Xu, Yiwenjie; Fu, Junjun; Maes, Joseph H R

2018-04-01

Previous studies examining effects of working memory (WM) updating training revealed mixed results. One factor that might modulate training gains, and possibly also transfer of those gains to non-trained cognitive tasks, is achievement motivation. In the present Studies 1 and 2, students with either a high (HAM) or low (LAM) achievement motivation completed a 14-day visuospatial WM updating training program. In Study 2, the students also performed a set of tasks measuring other executive functions and fluid intelligence prior to and after training. In both studies, the HAM students displayed a larger training gain than the LAM students. Study 2 revealed that after training, both groups showed better performance on the near-transfer but not far-transfer tasks. Importantly, the differential training gain was not associated with better post-training performance for the HAM compared to the LAM students on any of the transfer tasks. These results are taken to support a modulatory role of achievement motivation on WM training benefits, but not on transfer of those benefits to other tasks. Possible reasons for the general improvement on the near-transfer tasks and the absence of a modulatory role of achievement motivation on transfer-task performance are discussed.

Transfer Effects to a Multimodal Dual-Task after Working Memory Training and Associated Neural Correlates in Older Adults - A Pilot Study.

PubMed

Heinzel, Stephan; Rimpel, Jérôme; Stelzel, Christine; Rapp, Michael A

2017-01-01

Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60-72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality ( p < 0.05) and the auditory modality ( p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.

Transfer Effects to a Multimodal Dual-Task after Working Memory Training and Associated Neural Correlates in Older Adults – A Pilot Study

PubMed Central

Heinzel, Stephan; Rimpel, Jérôme; Stelzel, Christine; Rapp, Michael A.

2017-01-01

Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination. PMID:28286477

Contextual determinants of the social-transfer-of-learning effect.

PubMed

Milanese, Nadia; Iani, Cristina; Sebanz, Natalie; Rubichi, Sandro

2011-06-01

A recent study (Milanese et al. in Cogn 116(1):15-22, 2010) showed that performing a spatial compatibility task with incompatible S-R links (i.e., the practice task) alongside a co-actor eliminates the Simon effect in a subsequent joint Simon task (i.e., the transfer task). In the present study, we conducted three experiments to individuate which elements of the practice task need to remain constant for this social-transfer-of-learning to occur. In Experiment 1, participants performed the practice task alongside a co-actor and the Simon task with a different co-actor; in Experiment 2, they performed the practice task alongside a co-actor and the Simon task with the same co-actor after exchanging their seats. Results showed a modulation of the joint Simon effect in Experiment 1 only. In Experiment 2, we found a regular joint Simon effect. These results indicate that, while co-actor identity is not crucial, other elements of the context, such as keeping the same position across tasks, are necessary for the social-transfer-of-learning to occur. On the whole, our data suggest that the social-transfer-of-learning effect is not tuned to a specific co-actor and depends on spatial parameters of the practice and transfer tasks.

Role of the Methoxy Group in Immune Responses to mPEG-Protein Conjugates

PubMed Central

2012-01-01

Anti-PEG antibodies have been reported to mediate the accelerated clearance of PEG-conjugated proteins and liposomes, all of which contain methoxyPEG (mPEG). The goal of this research was to assess the role of the methoxy group in the immune responses to mPEG conjugates and the potential advantages of replacing mPEG with hydroxyPEG (HO-PEG). Rabbits were immunized with mPEG, HO-PEG, or t-butoxyPEG (t-BuO-PEG) conjugates of human serum albumin, human interferon-α, or porcine uricase as adjuvant emulsions. Assay plates for enzyme-linked immunosorbent assays (ELISAs) were coated with mPEG, HO-PEG, or t-BuO-PEG conjugates of the non-cross-reacting protein, porcine superoxide dismutase (SOD). In sera from rabbits immunized with HO-PEG conjugates of interferon-α or uricase, the ratio of titers of anti-PEG antibodies detected on mPEG-SOD over HO-PEG-SOD (“relative titer”) had a median of 1.1 (range 0.9–1.5). In contrast, sera from rabbits immunized with mPEG conjugates of three proteins had relative titers with a median of 3.0 (range 1.1–20). Analyses of sera from rabbits immunized with t-BuO-PEG-albumin showed that t-butoxy groups are more immunogenic than methoxy groups. Adding Tween 20 or Tween 80 to buffers used to wash the assay plates, as is often done in ELISAs, greatly reduced the sensitivity of detection of anti-PEG antibodies. Competitive ELISAs revealed that the affinities of antibodies raised against mPEG-uricase were c. 70 times higher for 10 kDa mPEG than for 10 kDa PEG diol and that anti-PEG antibodies raised against mPEG conjugates of three proteins had >1000 times higher affinities for albumin conjugates with c. 20 mPEGs than for analogous HO-PEG-albumin conjugates. Overall, these results are consistent with the hypothesis that antibodies with high affinity for methoxy groups contribute to the loss of efficacy of mPEG conjugates, especially if multiply-PEGylated. Using monofunctionally activated HO-PEG instead of mPEG in preparing conjugates for clinical use might decrease this undesirable effect. PMID:22332808

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study.

PubMed

Clowse, Megan Eb; Förger, Frauke; Hwang, Caroline; Thorp, John; Dolhain, Radboud Jem; van Tubergen, Astrid; Shaughnessy, Laura; Simpson, Jeff; Teil, Marie; Toublanc, Nathalie; Wang, Maggie; Hale, Thomas W

2017-11-01

Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. 19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants. When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc--free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. NCT02154425; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Using an embedded reality approach to improve test reliability for NHPT tasks.

PubMed

Bowler, M; Amirabdollahian, F; Dautenhahn, K

2011-01-01

Research into the use of haptic and virtual reality technologies has increased greatly over the past decade, in terms of both quality and quantity. Methods to utilise haptic and virtual technologies with currently existing techniques for assessing impairment are underway, and, due to the commercially available equipment, has found some success in the use of these methods for individuals who suffer upper limb impairment. This paper uses the clinically validated assessment technique for measuring motor impairment: the Nine Hole Peg Test and creates three tasks with different levels of realism. The efficacy of these tasks is discussed with particular attention paid to analysis in terms of removing factors that limit a virtual environment's use in a clinical setting, such as inter-subject variation. © 2011 IEEE

The US and Canadian Army Strategies: Failures in Understanding

DTIC Science & Technology

2003-04-07

methodology for identifying risks as associated with each core competency. Program Evaluation Groups (PEGs) perform the task of identifying competencies...stable group is completely immune to change. New ideas are insulated within the organization and allowed to develop. It features risk control as a...however, must be balanced with the ability to receive first-hand knowledge from the group with the greatest emotional stake in the future of the Army

Designing Tasks to Promote and Assess Mathematical Transfer in Primary School Children

ERIC Educational Resources Information Center

Clark, Julie; Page, Shaileigh; Thornton, Steve

2013-01-01

This study aims to design learning situations and tasks that promote and assess the capacity of primary school children to transfer mathematical knowledge to new contexts. We discuss previous studies investigating mathematical transfer, and particularly the strengths and limitations of tasks used to assess transfer in these studies. We describe…

Generalizing attentional control across dimensions and tasks: evidence from transfer of proportion-congruent effects.

PubMed

Wühr, Peter; Duthoo, Wout; Notebaert, Wim

2015-01-01

Three experiments investigated transfer of list-wide proportion congruent (LWPC) effects from a set of congruent and incongruent items with different frequency (inducer task) to a set of congruent and incongruent items with equal frequency (diagnostic task). Experiments 1 and 2 mixed items from horizontal and vertical Simon tasks. Tasks always involved different stimuli that varied on the same dimension (colour) in Experiment 1 and on different dimensions (colour, shape) in Experiment 2. Experiment 3 mixed trials from a manual Simon task with trials from a vocal Stroop task, with colour being the relevant stimulus in both tasks. There were two major results. First, we observed transfer of LWPC effects in Experiments 1 and 3, when tasks shared the relevant dimension, but not in Experiment 2. Second, sequential modulations of congruency effects transferred in Experiment 1 only. Hence, the different transfer patterns suggest that LWPC effects and sequential modulations arise from different mechanisms. Moreover, the observation of transfer supports an account of LWPC effects in terms of list-wide cognitive control, while being at odds with accounts in terms of stimulus-response (contingency) learning and item-specific control.

What's the Problem? Familiarity Working Memory, and Transfer in a Problem-Solving Task.

PubMed

Kole, James A; Snyder, Hannah R; Brojde, Chandra L; Friend, Angela

2015-01-01

The contributions of familiarity and working memory to transfer were examined in the Tower of Hanoi task. Participants completed 3 different versions of the task: a standard 3-disk version, a clothing exchange task that included familiar semantic content, and a tea ceremony task that included unfamiliar semantic content. The constraints on moves were equivalent across tasks, and each could be solved with the same sequence of movements. Working memory demands were manipulated by the provision of a (static or dynamic) visual representation of the problem. Performance was equivalent for the standard Tower of Hanoi and clothing exchange tasks but worse for the tea ceremony task, and it decreased with increasing working memory demands. Furthermore, the standard Tower of Hanoi task and clothing exchange tasks independently, additively, and equivalently transferred to subsequent tasks, whereas the tea ceremony task did not. The results suggest that both familiarity and working memory demands determine overall level of performance, whereas familiarity influences transfer.

Ultrafast spectroscopy on DNA-cleavage by endonuclease in molecular crowding.

PubMed

Singh, Priya; Choudhury, Susobhan; Dutta, Shreyasi; Adhikari, Aniruddha; Bhattacharya, Siddhartha; Pal, Debasish; Pal, Samir Kumar

2017-10-01

The jam-packed intracellular environments differ the activity of a biological macromolecule from that in laboratory environments (in vitro) through a number of mechanisms called molecular crowding related to structure, function and dynamics of the macromolecule. Here, we have explored the structure, function and dynamics of a model enzyme protein DNase I in molecular crowing of polyethylene glycol (PEG; MW 3350). We have used steady state and picosecond resolved dynamics of a well-known intercalator ethidium bromide (EB) in a 20-mer double-stranded DNA (dsDNA) to monitor the DNA-cleavage by the enzyme in absence and presence PEG. We have also labelled the enzyme by a well-known fluorescent probe 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) to study the molecular mechanism of the protein-DNA association through exited state relaxation of the probe in absence (dictated by polarity) and presence of EB in the DNA (dictated by Förster resonance energy transfer (FRET)). The overall and local structures of the protein in presence of PEG have been followed by circular dichroism and time resolved polarization gated spectroscopy respectively. The enhanced dynamical flexibility of protein in presence of PEG as revealed from excited state lifetime and polarization gated anisotropy of ANS has been correlated with the stronger DNA-binding for the higher nuclease activity. We have also used conventional experimental strategy of agarose gel electrophoresis to monitor DNA-cleavage and found consistent results of enhanced nuclease activities both on synthetic 20-mer oligonucleotide and long genomic DNA from calf thymus. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior

PubMed Central

Nakamura, Toru; Sato, Asako; Kitsukawa, Takashi; Momiyama, Toshihiko; Yamamori, Tetsuo; Sasaoka, Toshikuni

2014-01-01

Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous motor activity in the home cage environment for consecutive 5 days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT and mutant mice. PMID:25076876

Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior.

PubMed

Nakamura, Toru; Sato, Asako; Kitsukawa, Takashi; Momiyama, Toshihiko; Yamamori, Tetsuo; Sasaoka, Toshikuni

2014-01-01

Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous motor activity in the home cage environment for consecutive 5 days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT and mutant mice.

N-back versus Complex Span Working Memory Training.

PubMed

Blacker, Kara J; Negoita, Serban; Ewen, Joshua B; Courtney, Susan M

2017-12-01

Working memory (WM) is the ability to maintain and manipulate task-relevant information in the absence of sensory input. While its improvement through training is of great interest, the degree to which WM training transfers to untrained WM tasks (near transfer) and other untrained cognitive skills (far transfer) remains debated and the mechanism(s) underlying transfer are unclear. Here we hypothesized that a critical feature of dual n-back training is its reliance on maintaining relational information in WM. In Experiment 1, using an individual differences approach, we found evidence that performance on an n-back task was predicted by performance on a measure of relational WM (i.e., WM for vertical spatial relationships independent of absolute spatial locations); whereas the same was not true for a complex span WM task. In Experiment 2, we tested the idea that reliance on relational WM is critical to produce transfer from n-back but not complex span task training. Participants completed adaptive training on either a dual n-back task, a symmetry span task, or on a non-WM active control task. We found evidence of near transfer for the dual n-back group; however, far transfer to a measure of fluid intelligence did not emerge. Recording EEG during a separate WM transfer task, we examined group-specific, training-related changes in alpha power, which are proposed to be sensitive to WM demands and top-down modulation of WM. Results indicated that the dual n-back group showed significantly greater frontal alpha power after training compared to before training, more so than both other groups. However, we found no evidence of improvement on measures of relational WM for the dual n-back group, suggesting that near transfer may not be dependent on relational WM. These results suggest that dual n-back and complex span task training may differ in their effectiveness to elicit near transfer as well as in the underlying neural changes they facilitate.

An Acoustofluidic Micromixer via Bubble Inception and Cavitation from Microchannel Sidewalls

PubMed Central

2015-01-01

During the deep reactive ion etching process, the sidewalls of a silicon mold feature rough wavy structures, which can be transferred onto a polydimethylsiloxane (PDMS) microchannel through the soft lithography technique. In this article, we utilized the wavy structures of PDMS microchannel sidewalls to initiate and cavitate bubbles in the presence of acoustic waves. Through bubble cavitation, this acoustofluidic approach demonstrates fast, effective mixing in microfluidics. We characterized its performance by using viscous fluids such as poly(ethylene glycol) (PEG). When two PEG solutions with a resultant viscosity 54.9 times higher than that of water were used, the mixing efficiency was found to be 0.92, indicating excellent, homogeneous mixing. The acoustofluidic micromixer presented here has the advantages of simple fabrication, easy integration, and capability to mix high-viscosity fluids (Reynolds number: ∼0.01) in less than 100 ms. PMID:24754496

Mussel-Inspired Dopamine and Carbon Nanotube Leading to a Biocompatible Self-Rolling Conductive Hydrogel Film.

PubMed

Jiang, Junzi; Huang, Yong; Wang, Yitian; Xu, Hui; Xing, Malcolm; Zhong, Wen

2017-08-18

We report a novel self-rolling, conductive, and biocompatible multiwall carbon nanotube (MWCNT)-dopamine-polyethylene glycol (PEG) hydrogel film. The gel can self-fold into a thin tube when it is transferred from a glass slide to an aqueous environment, regardless of the concentrations of the MWCNT. The film presents a highly organized pattern, which results from the self-assembly of hydrophilic dopamine and hydrophobic carbon nanotubes. By exploring the biomedical potential, we found that MWCNT-included rolled film is nontoxic and can promote cell growth. For further functional verification by qPCR (quantitative polymerase chain reaction), bone marrow derived mesenchymal cells present higher levels of osteogenic differentiations in response to a higher concentration of CNTs. The results suggest that the self-rolling, conductive CNT-dopamine-PEG hydrogel could have multiple potentials, including biomedical usage and as a conductive biosensor.

Effects of task repetition but no transfer of inhibitory control training in healthy adults.

PubMed

Talanow, Tobias; Ettinger, Ulrich

2018-06-01

Executive functions (EFs) comprise the updating, shifting and inhibition dimensions. According to the Unity and Diversity Model, the inhibition dimension is fully accounted for by a general EFs factor. This suggests that training of inhibition should transfer, in part, to updating and shifting. Therefore, we tested the effectiveness of a three-week inhibition training (high-conflict Stroop task) and explored near transfer effects to an untrained inhibition task (antisaccade task) and far transfer effects to untrained tasks demanding task-set shifting (number-letter-task), working memory updating (n-back task) and planning abilities (Stockings of Cambridge task). We employed a randomized pretest/treatment/posttest study design in n = 102 healthy young adults, assigned to an intensive Stroop training (n = 38), an active control condition (n = 34) or no training intervention (n = 30). In the Stroop training group, Stroop performance improved with practice, while performance in the active control group remained unchanged. The Stroop training group showed improvements in overall Stroop task performance from pretest to posttest, but we observed neither near nor far transfer effects. Additionally, specifically stronger gains on incongruent Stroop trials compared to congruent trials were observed in the Stroop training group when color bar trials were excluded from the pretest-posttest-analysis. Generally, there were substantial improvements from pretest to posttest independent of training condition in all transfer tasks. In sum, our data do not support the existence of transfer effects from inhibition training in healthy young adults. Copyright © 2018 Elsevier B.V. All rights reserved.

Perceptual learning of basic visual features remains task specific with Training-Plus-Exposure (TPE) training.

PubMed

Cong, Lin-Juan; Wang, Ru-Jie; Yu, Cong; Zhang, Jun-Yun

2016-01-01

Visual perceptual learning is known to be specific to the trained retinal location, feature, and task. However, location and feature specificity can be eliminated by double-training or TPE training protocols, in which observers receive additional exposure to the transfer location or feature dimension via an irrelevant task besides the primary learning task Here we tested whether these new training protocols could even make learning transfer across different tasks involving discrimination of basic visual features (e.g., orientation and contrast). Observers practiced a near-threshold orientation (or contrast) discrimination task. Following a TPE training protocol, they also received exposure to the transfer task via performing suprathreshold contrast (or orientation) discrimination in alternating blocks of trials in the same sessions. The results showed no evidence for significant learning transfer to the untrained near-threshold contrast (or orientation) discrimination task after discounting the pretest effects and the suprathreshold practice effects. These results thus do not support a hypothetical task-independent component in perceptual learning of basic visual features. They also set the boundary of the new training protocols in their capability to enable learning transfer.

The effect on colon visualization during colonoscopy of the addition of simethicone to polyethylene glycol-electrolyte solution: a randomized single-blind study.

PubMed

Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David

2012-11-29

Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38%; P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations.

The Effect on Colon Visualization During Colonoscopy of the Addition of Simethicone to Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study

PubMed Central

Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David

2012-01-01

OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. RESULTS: One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38% P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. CONCLUSIONS: Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations. PMID:23238113

Addition of simethicone improves small bowel capsule endoscopy visualisation quality.

PubMed

Krijbolder, M S; Grooteman, K V; Bogers, S K; de Jong, D J

2018-01-01

Small bowel capsule endoscopy (SBCE) is an important diagnostic tool for small-bowel diseases but its quality may be hampered by intraluminal gas. This study evaluated the added value of the anti-foaming agent, simethicone, to a bowel preparation with polyethylene glycol (PEG) on the quality of small bowel visualisation and its use in the Netherlands. This was a retrospective, single-blind, cohort study. Patients in the PEG group only received PEG prior to SBCE. Patients in the PEG-S group ingested additional simethicone. Two investigators assessed the quality of small-bowel visualisation using a four-point scale for 'intraluminal gas' and 'faecal contamination'. By means of a survey, the use of anti-foaming agents was assessed in a random sample of 16 Dutch hospitals performing SBCE. The quality of small bowel visualisation in the PEG group (n = 33) was significantly more limited by intraluminal gas when compared with the PEG-S group (n = 31): proximal segment 83.3% in PEG group vs. 18.5% in PEG-S group (p < 0.01), distal segment 66.7% vs. 18.5% respectively (p < 0.01). No difference was observed in the amount of faecal contamination (proximal segment 80.0% PEG vs. 59.3% PEG-S, p = 0.2; distal segment 90.0% PEG vs. 85.2% PEG-S, p = 0.7), mean small bowel transit times (4.0 PEG vs. 3.9 hours PEG-S, p = 0.7) and diagnostic yield (43.3% PEG vs. 22.2% PEG-S, p = 0.16). Frequency of anti-foaming agent use in the Netherlands was low (3/16, 18.8%). Simethicone is of added value to a PEG bowel preparation in improving the quality of visualisation of the small bowel by reducing intraluminal gas. At present, the use of anti-foaming agents in SBCE preparation is not standard practice in the Netherlands.

Transfer of learning between unimanual and bimanual rhythmic movement coordination: transfer is a function of the task dynamic.

PubMed

Snapp-Childs, Winona; Wilson, Andrew D; Bingham, Geoffrey P

2015-07-01

Under certain conditions, learning can transfer from a trained task to an untrained version of that same task. However, it is as yet unclear what those certain conditions are or why learning transfers when it does. Coordinated rhythmic movement is a valuable model system for investigating transfer because we have a model of the underlying task dynamic that includes perceptual coupling between the limbs being coordinated. The model predicts that (1) coordinated rhythmic movements, both bimanual and unimanual, are organised with respect to relative motion information for relative phase in the coupling function, (2) unimanual is less stable than bimanual coordination because the coupling is unidirectional rather than bidirectional, and (3) learning a new coordination is primarily about learning to perceive and use the relevant information which, with equal perceptual improvement due to training, yields equal transfer of learning from bimanual to unimanual coordination and vice versa [but, given prediction (2), the resulting performance is also conditioned by the intrinsic stability of each task]. In the present study, two groups were trained to produce 90° either unimanually or bimanually, respectively, and tested in respect to learning (namely improved performance in the trained 90° coordination task and improved visual discrimination of 90°) and transfer of learning (to the other, untrained 90° coordination task). Both groups improved in the task condition in which they were trained and in their ability to visually discriminate 90°, and this learning transferred to the untrained condition. When scaled by the relative intrinsic stability of each task, transfer levels were found to be equal. The results are discussed in the context of the perception-action approach to learning and performance.

Using dual tasks to test immediate transfer of training between naturalistic movements: a proof-of-principle study.

PubMed

Schaefer, Sydney Y; Lang, Catherine E

2012-01-01

Theories of motor learning predict that training a movement reduces the amount of attention needed for its performance (i.e., more automatic). If training one movement transfers, then the amount of attention needed for performing a second movement should also be reduced, as measured under dual task conditions. The authors' purpose was to test whether dual task paradigms are feasible for detecting transfer of training between two naturalistic movements. Immediately following motor training, subjects improved performance of a second untrained movement under single and dual task conditions. Subjects with no training did not. Improved performance in the untrained movement was likely due to transfer, and suggests that dual tasks may be feasible for detecting transfer between naturalistic actions.

Age Differences in the Transfer and Maintenance of Practice-Induced Improvements in Task Switching: The Impact of Working-Memory and Inhibition Demands

PubMed Central

Kray, Jutta; Fehér, Balázs

2017-01-01

Recent aging studies on training in task switching found that older adults showed larger improvements to an untrained switching task as younger adults do. However, less clear is what type of cognitive control processes can explain these training gains as participants were trained with a particular type of switching task including bivalent stimuli, requiring high inhibition demands, and no task cues helping them keeping track of the task sequence, and by this, requiring high working-memory (WM) demands. The aims of this study were first to specify whether inhibition, WM, or switching demands are critical for the occurrence of transfer and whether this transfer depends on the degree of overlap between training and transfer situation; and second to assess whether practiced-induced gains in task switching can be maintained over a longer period of time. To this end, we created five training conditions that varied in switching (switching vs. single task training), inhibition (switching training with bivalent or univalent stimuli), and WM demands (switching training with or without task cues). We investigated 81 younger adults and 82 older adults with a pretest-training-posttest design and a follow-up measurement after 6 months. Results indicated that all training and age groups showed improvements in task switching and a differential effect of training condition on improvements to an untrained switching task in younger and older adults. For younger adults, we found larger improvements in task switching for the switching groups than the single-task training group independently of inhibition and WM demands, suggesting that practice in switching is most critical. However, these benefits disappeared after 6 months. In contrast, for older adults training groups practicing task switching under high inhibition demands showed larger improvements to untrained switching tasks than the other groups. Moreover, these benefits were maintained over time. We also found that the transfer of benefits in task switching was larger with greater overlap between training and transfer situation. However, results revealed no evidence for transfer to other untrained cognitive task. Overall, the findings suggest that training in resolving interference while switching between two tasks is most critical for the occurrence of transfer in the elderly. PMID:28367135

Preparation and investigation of acetyl salicylic acid-caffeine complex for rectal administration.

PubMed

Fouad, Ehab A; El-Badry, Mahmoud; Alanazi, Fars K; Arafah, Maha M; Al-Ashban, Riyadh; Alsarra, Ibrahim A

2010-06-01

An acetyl salicylic acid-caffeine complex was prepared and evaluated for the potential use in rectal administration. The results revealed the formation of a complex between acetyl salicylic acid and caffeine in a 1:1 molar ratio by a charge transfer mechanism. The effects of acetyl salicylic acid and complex on the rectal tissues showed destruction in the mucosal epithelium in case of acetyl salicylic acid; however, no change in the rectal tissues was noticed upon the administration of the complex. The effect of suppository bases on the release of the complex was studied using Witepsol H15 as fatty base and polyethylene glycols (PEG) 1000 and 4000 as a water soluble suppository base. The release profiles of acetyl salicylic acid and the complex were faster from PEG than from that of Witepsol H15. The percent release for the complex and acetyl salicylic acid from PEG base were 45.8, and 34.9%, respectively. However, it was 8.7 and 7.8%, respectively, from Witepsol H15 fatty base. The release kinetic was found to follow the non-Fickian diffusion model for complex from the suppository bases. It was concluded that acetyl salicylic acid caffeine complex can be used safely for rectal administration.

Preparation and investigation of acetyl salicylic acid-caffeine complex for rectal administration.

PubMed

Fouad, Ehab A; El-Badry, Mahmoud; Alanazi, Fars K; Arafah, Maha M; Al-Ashban, Riyadh; Alsarra, Ibrahim A

2009-07-30

An acetyl salicylic acid-caffeine complex was prepared and evaluated for the potential use in rectal administration. The results revealed the formation of a complex between acetyl salicylic acid and caffeine in a 1:1 molar ratio by a charge transfer mechanism. The effects of acetyl salicylic acid and complex on the rectal tissues showed destruction in the mucosal epithelium in case of acetyl salicylic acid; however, no change in the rectal tissues was noticed upon the administration of the complex. The effect of suppository bases on the release of the complex was studied using Witepsol H15 as fatty base and polyethylene glycols (PEG) 1000 and 4000 as a water soluble suppository base. The release profiles of acetyl salicylic acid and the complex were faster from PEG than from that of Witepsol H15. The percent release for the complex and acetyl salicylic acid from PEG base were 45.8, and 34.9%, respectively. However, it was 8.7 and 7.8%, respectively, from Witepsol H15 fatty base. The release kinetic was found to follow the non-Fickian diffusion model for complex from the suppository bases. It was concluded that acetyl salicylic acid caffeine complex can be used safely for rectal administration.

Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

PubMed

Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

2017-11-01

Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

Inhibition Plasticity in Older Adults: Practice and Transfer Effects Using a Multiple Task Approach.

PubMed

Wilkinson, Andrea J; Yang, Lixia

2016-01-01

OBJECTIVE. To examine plasticity of inhibition, as indexed by practice effects of inhibition tasks and the associated transfer effects, using a multiple task approach in healthy older adults. METHOD. Forty-eight healthy older adults were evenly assigned to either a practice group or a no-contact control group. All participants completed pretest (2.5 hours) and posttest (2 hours) sessions, with a 2-week interval in between. During the 2-week interval, only the practice group completed six 30-minute practice sessions (three sessions per week for two consecutive weeks) of three lab-based inhibition tasks. RESULTS. All three inhibition tasks demonstrated significant improvement across practice sessions, suggesting practice-induced plasticity. The benefit, however, only transferred to near-near tasks. The results are inconclusive with regard to the near-far and far-far transfer effects. DISCUSSION. This study further extends literature on practice effects of inhibition in older adults by using a multiple task approach. Together with previous work, the current study suggests that older adults are able to improve inhibition performance through practice and transfer the practice gains to tasks that overlap in both target cognitive ability and task structure (i.e., near-near tasks).

Inhibition Plasticity in Older Adults: Practice and Transfer Effects Using a Multiple Task Approach

PubMed Central

Wilkinson, Andrea J.; Yang, Lixia

2016-01-01

Objective. To examine plasticity of inhibition, as indexed by practice effects of inhibition tasks and the associated transfer effects, using a multiple task approach in healthy older adults. Method. Forty-eight healthy older adults were evenly assigned to either a practice group or a no-contact control group. All participants completed pretest (2.5 hours) and posttest (2 hours) sessions, with a 2-week interval in between. During the 2-week interval, only the practice group completed six 30-minute practice sessions (three sessions per week for two consecutive weeks) of three lab-based inhibition tasks. Results. All three inhibition tasks demonstrated significant improvement across practice sessions, suggesting practice-induced plasticity. The benefit, however, only transferred to near-near tasks. The results are inconclusive with regard to the near-far and far-far transfer effects. Discussion. This study further extends literature on practice effects of inhibition in older adults by using a multiple task approach. Together with previous work, the current study suggests that older adults are able to improve inhibition performance through practice and transfer the practice gains to tasks that overlap in both target cognitive ability and task structure (i.e., near-near tasks). PMID:26885407

Working memory training and transfer in older adults: effects of age, baseline performance, and training gains.

PubMed

Zinke, Katharina; Zeintl, Melanie; Rose, Nathan S; Putzmann, Julia; Pydde, Andrea; Kliegel, Matthias

2014-01-01

Recent studies suggest that working memory training may benefit older adults; however, findings regarding training and transfer effects are mixed. The current study aimed to investigate the effects of a process-based training intervention in a diverse sample of older adults and explored possible moderators of training and transfer effects. For that purpose, 80 older adults (65-95 years) were assigned either to a training group that worked on visuospatial, verbal, and executive working memory tasks for 9 sessions over 3 weeks or to a control group. Performance on trained and transfer tasks was assessed in all participants before and after the training period, as well as at a 9-month follow-up. Analyses revealed significant training effects in all 3 training tasks in trained participants relative to controls, as well as near transfer to a verbal working memory task and far transfer to a fluid intelligence task. Encouragingly, all training effects and the transfer effect to verbal working memory were stable at the 9-month follow-up session. Further analyses revealed that training gains were predicted by baseline performance in training tasks and (to a lesser degree) by age. Gains in transfer tasks were predicted by age and by the amount of improvement in the trained tasks. These findings suggest that cognitive plasticity is preserved over a large range of old age and that even a rather short training regime can lead to (partly specific) training and transfer effects. However, baseline performance, age, and training gains moderate the amount of plasticity. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The U.S. and Canadian Army Strategies: Failures in Understanding

DTIC Science & Technology

2003-09-01

competency. Program Evaluation Groups (PEGs) perform the task of identifying competencies required to meet particular demands and applying resources to...180 This requires clear delineation and different roles; this does not mean the stable group is completely immune to change. New ideas are insulated...first-hand knowledge from the group with the greatest emotional stake in the future of the Army―those at the coal-face. This same group is most

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2014-09-01

specific membrane antigen ( PSMA ) for prostate cancer theranostic application. Task 5 (Months 9 – 30): In vivo and PET/CT imaging evaluation of the...separate the entire synthesis into several subunits as shown in Scheme 1. The PSMA targeting ligand 4 has been synthesized in a conventional chemistry way...6]. To retain the PSMA targeting ligand affinity after integration into the MDCs, a PEG5 and a Boc-lysine linker has been introduced to form

Self-guided strategy-adaption training for older adults: Transfer effects to everyday tasks.

PubMed

Bottiroli, Sara; Cavallini, Elena; Dunlosky, John; Vecchi, Tomaso; Hertzog, Christopher

2017-09-01

The goal of the present research was to examine the potential of a learner-oriented approach to improving older adults' performance in tasks that are similar to real-life situations that require strategic deployment of cognitive resources. A crucial element of this approach involves encouraging older adults to explicitly analyze tasks to consider how to adapt trained skills to a new task context. In an earlier study, a specialist-directed intervention produced training gains and transfer to some untrained memory tasks. In the present study, older adults received a manual instructing them about principles of task analysis, two memory strategies, and strategy adaptation. Self-guided strategy-adaption training involved practicing some memory tasks as well as instructions on how the trained skills could be applied to new tasks that were not practiced. The criterion tasks involved practice tasks, non-practiced tasks that were discussed in the manual, and transfer tasks that were never mentioned in the manual. Two of the tests were from the Everyday Cognition Battery (inductive reasoning and working memory). As compared to a waiting-list control group, older adults assigned to self-guided strategy-adaption training showed memory improvements on tasks that were practiced or discussed during training. Most important, the learner-oriented approach produced transfer to the everyday tasks. Our findings show the potential of instructing task appraisal processes as a basis for fostering transfer, including improving older adults' performance in simulated everyday tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

2 L PEG plus ascorbic acid versus 4 L PEG plus simethicon for colonoscopy preparation: a randomized single-blind clinical trial.

PubMed

Gentile, Maurizio; De Rosa, Michele; Cestaro, Giovanni; Forestieri, Pietro

2013-06-01

The 2 L polyethylene glycol (PEG) lavage solution has been proved to be similarly safe and effective as 4 L PEG formulations, in spite of the reduced volume. To compare low-volume PEG-based solution combined with ascorbic acid with high-volume PEG-based solution combined with simethicon in terms of efficacy and patient tolerability. This was a single-blind prospective randomized trial. Patients were randomized to receive either 2 L PEG plus ascorbic acid (PEG+Asc) or 4 L PEG plus simethicon (PEG+Sim). The primary endpoint was overall colon cleansing evaluation, assessed by blinded investigators using Aronchick score. Secondary end points included patient compliance and tolerability and adverse events. Sixty patients received PEG+Asc and 60 received PEG+Sim. Overall bowel cleansing score was considered adequate in 81.67% of the PEG+Asc and 80% of the PEG+Sim groups, respectively. Excellent and good ratings were recorded in 11.6% and 38.3% receiving PEG+Asc as compared with 26.6% and 23.3% of patients receiving PEG+Sim. Patient tolerability and safety were similar with both the preparations. According to our data, low-volume PEG+Asc has comparable efficacy, safety, and tolerability as high-volume PEG+Sim; therefore, it can be considered as a good alternative solution for bowel preparation. More improvements are necessary to achieve the target of a perfect preparation.

Integrated Design of a Telerobotic Workstation

NASA Technical Reports Server (NTRS)

Rochlis, Jennifer L.; Clarke, John-Paul

2001-01-01

The experiments described in this paper are part of a larger joint MIT/NASA research effort that focuses on the development of a methodology for designing and evaluating integrated interfaces for highly dexterous and multi-functional telerobots. Specifically, a telerobotic workstation is being designed for an Extravehicular Activity (EVA) anthropomorphic space station telerobot. Previous researchers have designed telerobotic workstations based upon performance of discrete subsets of tasks (for example, peg-in-hole, tracking, etc.) without regard for transitions that operators go through between tasks performed sequentially in the context of larger integrated tasks. The exploratory research experiments presented here took an integrated approach and assessed how subjects operating a full-immersion telerobot perform during the transitions between sub-tasks of two common EVA tasks. Preliminary results show that up to 30% of total task time is spent gaining and maintaining Situation Awareness (SA) of their task space and environment during transitions. Although task performance improves over the two trial days, the percentage of time spent on SA remains the same. This method identifies areas where workstation displays and feedback mechanisms are most needed to increase operator performance and decrease operator workload - areas that previous research methods have not been able to address.

Formation of protein complex with the aid of polyethylene glycol for deproteinized natural rubber latex

NASA Astrophysics Data System (ADS)

Wei, Lim Keuw; Ing, Wong Kwee; Badri, Khairiah Haji; Ban, Wong Chong

2013-11-01

The effect of polyethylene glycol (PEG) as a deproteinizing agent in commercial natural rubber latex (NRL) onto the physicochemical properties of the NRL was investigated. Three types of PEG were used namely PEG200, PEG4000 and PEG20000 (molecular weight of 200, 4000 and 20000 g/mol respectively). The optimum amount of PEG in NRL was determined from viscosity changes, protein content and Fourier Transform Infrared spectroscopy. Level of protein reduction was affected by molecular weight of PEG. The addition of PEG in NRL reduced the protein content of NRL (3.30 %) to the lowest (2.01 %) at 0.40 phr of PEG200 due to more attractive hydrophobic interactions between short chains PEG compared to PEG4000 (2.24%) and PEG20000 (2.15%). This was verified through FTIR spectroscopy analysis by observing the primary and secondary amide peak where PEG4000 has lesser absorption at the region compared to with PEG20000.

Limited Benefits of Heterogeneous Dual-Task Training on Transfer Effects in Older Adults.

PubMed

Lussier, Maxime; Brouillard, Philippe; Bherer, Louis

2017-09-01

It has often been reported that cognitive training has limited transfer effects. The present study addresses training context variability as a factor that could increase transfer effects, as well as the manifestation through time of transfer effects. Fifty-eight older adults were assigned to an active placebo or two dual-task training conditions, one in which the training context varies between sessions (heterogeneous training) and the other in a fixed training context (homogeneous training). Transfer was assessed with near and far-modality transfer tasks. Results show that heterogeneous and homogeneous training led to larger near-modality transfer effects than an active placebo (computer lessons). Transfer effects were roughly comparable in both training groups, but heterogeneous training led to a steeper improvement of the dual-task coordination learning curve within training sessions. Also, results indicated that dual-task cost did not improve in the active placebo group from the pre- to the post-training sessions. Heterogeneous training showed modest advantages over homogeneous training. Results also suggest that transfer effects on dual-task cost induced by training take place early on in the post-training session. These findings provide valuable insights on benefits arising from variability in the training protocol for maximizing transfer effects. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Training and transfer effects of interference control training in children and young adults.

PubMed

Zhao, Xin; Jia, Lina

2018-04-24

Many studies have examined transfer of working memory (WM) training improvements to non-trained cognitive tasks, with largely disappointing results. Interference control has been suggested to be a central feature of WM. However, studies examining transfer effects of a training program exclusively and directly targeting interference control are lacking. Forty-one 10‒12 year-old children and 47 19‒24 year-old adults were assigned to an adaptive interference control training or active control condition. Transfer of training effects to tasks measuring interference control, response inhibition, WM updating, task-switching, and non-verbal fluid intelligence were assessed during a 3-month follow-up session and/or an immediate post-training session. Substantial evidence of training improvements and a positive transfer effect to a non-trained interference control task were observed for both age groups. Marginal evidence for beneficial transfer of training effects for the trained compared to non-trained participants was found for a WM task for both age groups, and for the children for another interference control task and a response inhibition task. However, these transfer effects were absent during the 3-month follow-up measurement. These results suggest some potential for interference control training programs to enhance aspects of cognitive functioning, with some evidence for a more wide-spread, but short-lived, transfer for children compared to adults.

Generalization of Auditory Sensory and Cognitive Learning in Typically Developing Children.

PubMed

Murphy, Cristina F B; Moore, David R; Schochat, Eliane

2015-01-01

Despite the well-established involvement of both sensory ("bottom-up") and cognitive ("top-down") processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported "far-transfer" to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research is required to investigate the effects of various stimuli and lengths of training on the generalization of sensory and cognitive learning to literacy skills.

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate)

NASA Astrophysics Data System (ADS)

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO3H2) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y2O3 nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO3H2 (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO3H2 was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO3H2) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y2O3 nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO3H2 (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO3H2 was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection. Electronic supplementary information (ESI) available: 1H-NMR spectra of PEG-b-PCMS, PEG-b-PDEVBP and PEG-b-PVBP, 31P-NMR spectra of PEG-b-PDEVBP and PEG-b-PVBP, schematic representation of PEG-PO3H2 synthesis, 1H-NMR spectra of PEG-PO3Et2 and PEG-PO3H2, FT-IR spectra of YNP samples, PEG brush density on the YNP surface, and size distribution of YNP samples under acidic conditions are described. See DOI: 10.1039/c1nr10466g

Developments of new force reflecting control schemes and an application to a teleoperation training simulator

NASA Technical Reports Server (NTRS)

Kim, Won S.

1992-01-01

Two schemes of force reflecting control, position-error based force reflection and low-pass-filtered force reflection, both combined with shared compliance control, were developed for dissimilar master-slave arms. These schemes enabled high force reflection gains, which were not possible with a conventional scheme when the slave arm was much stiffer than the master arm. The experimental results with a peg-in-hole task indicated that the newly force reflecting control schemes combined with compliance control resulted in best task performances. As a related application, a simulated force reflection/shared compliance control teleoperation trainer was developed that provided the operator with the feel of kinesthetic force virtual reality.

Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trumbo, Michael C.; Matzen, Laura E.; Coffman, Brian A.

Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In eachmore » experiment, participants received either active (2.0 mA) or sham (0.1 mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). Here, in Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used.« less

Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer

DOE PAGES

Trumbo, Michael C.; Matzen, Laura E.; Coffman, Brian A.; ...

2016-10-15

Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In eachmore » experiment, participants received either active (2.0 mA) or sham (0.1 mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). Here, in Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used.« less

Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer.

PubMed

Trumbo, Michael C; Matzen, Laura E; Coffman, Brian A; Hunter, Michael A; Jones, Aaron P; Robinson, Charles S H; Clark, Vincent P

2016-12-01

Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In each experiment, participants received either active (2.0mA) or sham (0.1mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). In Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using dual tasks to test immediate transfer of training between naturalistic movements: A proof-of-principle study

PubMed Central

Schaefer, Sydney Y.; Lang, Catherine E.

2012-01-01

Theories of motor learning predict that training a movement reduces the amount of attention needed for its performance (i.e. more automatic). If training one movement transfers, then the amount of attention needed for performing a second movement should also be reduced, as measured under dual task conditions. The purpose of this study was to test whether dual task paradigms are feasible for detecting transfer of training between two naturalistic movements. Immediately following motor training, subjects improved performance of a second untrained movement under both single and dual task conditions. Subjects with no training did not. Improved performance in the untrained movement was likely due to transfer, and suggests that dual tasks may be feasible for detecting transfer between naturalistic actions. PMID:22934682

Perceptual learning of basic visual features remains task specific with Training-Plus-Exposure (TPE) training

PubMed Central

Cong, Lin-Juan; Wang, Ru-Jie; Yu, Cong; Zhang, Jun-Yun

2016-01-01

Visual perceptual learning is known to be specific to the trained retinal location, feature, and task. However, location and feature specificity can be eliminated by double-training or TPE training protocols, in which observers receive additional exposure to the transfer location or feature dimension via an irrelevant task besides the primary learning task Here we tested whether these new training protocols could even make learning transfer across different tasks involving discrimination of basic visual features (e.g., orientation and contrast). Observers practiced a near-threshold orientation (or contrast) discrimination task. Following a TPE training protocol, they also received exposure to the transfer task via performing suprathreshold contrast (or orientation) discrimination in alternating blocks of trials in the same sessions. The results showed no evidence for significant learning transfer to the untrained near-threshold contrast (or orientation) discrimination task after discounting the pretest effects and the suprathreshold practice effects. These results thus do not support a hypothetical task-independent component in perceptual learning of basic visual features. They also set the boundary of the new training protocols in their capability to enable learning transfer. PMID:26873777

Construction of Hierarchical Polymer Brushes on Upconversion Nanoparticles via NIR-Light-Initiated RAFT Polymerization.

PubMed

Xie, Zhongxi; Deng, Xiaoran; Liu, Bei; Huang, Shanshan; Ma, Pingan; Hou, Zhiyao; Cheng, Ziyong; Lin, Jun; Luan, Shifang

2017-09-13

Photoinduced reversible addition-fragmentation chain transfer (RAFT) polymerization generally adopts high-energy ultraviolet (UV) or blue light. In combination with photoredox catalyst, the excitation light wavelength was extended to the visible and even near-infrared (NIR) region for photoinduced electron transfer RAFT polymerization. In this report, we introduce for the first time a surface NIR-light-initiated RAFT polymerization on upconversion nanoparticles (UCNPs) without adding any photocatalyst and construct a functional inorganic core/polymer shell nanohybrid for application in cancer theranostics. The multilayer core-shell UCNPs (NaYF 4 :Yb/Tm@NaYbF 4 :Gd@NaNdF 4 :Yb@NaYF 4 ), with surface anchorings of chain transfer agents, can serve as efficient NIR-to-UV light transducers for initiating the RAFT polymerization. A hierarchical double block copolymer brush, consisting of poly(acrylic acid) (PAA) and poly(oligo(ethylene oxide)methacrylate-co-2-(2-methoxy-ethoxy)ethyl methacrylate) (PEG for short), was grafted from the surface in sequence. The targeting arginine-glycine-aspartic (RGD) peptide was modified at the end of the copolymer through the trithiolcarbonate end group. After loading of doxorubicin, the UCNPs@PAA-b-PEG-RGD exhibited an enhanced U87MG cancer cell uptake efficiency and cytotoxicity. Besides, the unique upconversion luminescence of the nanohybrids was used for the autofluoresence-free cell imaging and labeling. Therefore, our strategy verified that UCNPs could efficiently activate RAFT polymerization by NIR photoirradiation and construct the complex nanohybrids, exhibiting prospective biomedical applications due to the low phototoxicity and deep penetration of NIR light.

PEG and mPEG-anthracene induce DNA condensation and particle formation.

PubMed

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2011-08-18

In this study, we investigated the binding of DNA with poly(ethylene glycol) (PEG) of different sizes and compositions such as PEG 3350, PEG 6000, and mPEG-anthracene in aqueous solution at physiological conditions. The effects of size and composition on DNA aggregation and condensation as well as conformation were determined using Fourier transform infrared (FTIR), UV-visible, CD, fluorescence spectroscopic methods and atomic force microscopy (AFM). Structural analysis showed moderate complex formation for PEG 3350 and PEG 6000 and weaker interaction for mPE-anthracene-DNA adducts with both hydrophilic and hydrophobic contacts. The order of ± stability of the complexes formed is K(PEG 6000) = 1.5 (±0.4) × 10(4) M(-1) > K(PEG 3350) = 7.9 (±1) × 10(3) M(-1) > K(m(PEG-anthracene))= 3.6 (±0.8) × 10(3) M(-1) with nearly 1 bound PEG molecule per DNA. No B-DNA conformational changes were observed, while DNA condensation and particle formation occurred at high PEG concentration.

Transfer of short-term motor learning across the lower limbs as a function of task conception and practice order.

PubMed

Stöckel, Tino; Wang, Jinsung

2011-11-01

Interlimb transfer of motor learning, indicating an improvement in performance with one limb following training with the other, often occurs asymmetrically (i.e., from non-dominant to dominant limb or vice versa, but not both). In the present study, we examined whether interlimb transfer of the same motor task could occur asymmetrically and in opposite directions (i.e., from right to left leg vs. left to right leg) depending on individuals' conception of the task. Two experimental conditions were tested: In a dynamic control condition, the process of learning was facilitated by providing the subjects with a type of information that forced them to focus on dynamic features of a given task (force impulse); and in a spatial control condition, it was done with another type of information that forced them to focus on visuomotor features of the same task (distance). Both conditions employed the same leg extension task. In addition, a fully-crossed transfer paradigm was used in which one group of subjects initially practiced with the right leg and were tested with the left leg for a transfer test, while the other group used the two legs in the opposite order. The results showed that the direction of interlimb transfer varied depending on the condition, such that the right and the left leg benefited from initial training with the opposite leg only in the spatial and the dynamic condition, respectively. Our finding suggests that manipulating the conception of a leg extension task has a substantial influence on the pattern of interlimb transfer in such a way that the direction of transfer can even be opposite depending on whether the task is conceived as a dynamic or spatial control task. Copyright © 2011 Elsevier Inc. All rights reserved.

Training attentional control in older adults

PubMed Central

MacKay-Brandt, Anna

2013-01-01

Recent research has demonstrated benefits for older adults from training attentional control using a variable priority strategy, but the construct validity of the training task and the degree to which benefits of training transfer to other contexts are unclear. The goal of this study was to characterize baseline performance on the training task in a sample of 105 healthy older adults and to test for transfer of training in a subset (n = 21). Training gains after 5 days and extent of transfer was compared to another subset (n = 20) that served as a control group. Baseline performance on the training task was characterized by a two-factor model of working memory and processing speed. Processing speed correlated with the training task. Training gains in speed and accuracy were reliable and robust (ps <.001, η2 = .57 to .90). Transfer to an analogous task was observed (ps <.05, η2 = .10 to .17). The beneficial effect of training did not translate to improved performance on related measures of processing speed. This study highlights the robust effect of training and transfer to a similar context using a variable priority training task. Although processing speed is an important aspect of the training task, training benefit is either related to an untested aspect of the training task or transfer of training is limited to the training context. PMID:21728889

Cross-domain and multi-task transfer learning of deep convolutional neural network for breast cancer diagnosis in digital breast tomosynthesis

NASA Astrophysics Data System (ADS)

Samala, Ravi K.; Chan, Heang-Ping; Hadjiiski, Lubomir; Helvie, Mark A.; Richter, Caleb; Cha, Kenny

2018-02-01

We propose a cross-domain, multi-task transfer learning framework to transfer knowledge learned from non-medical images by a deep convolutional neural network (DCNN) to medical image recognition task while improving the generalization by multi-task learning of auxiliary tasks. A first stage cross-domain transfer learning was initiated from ImageNet trained DCNN to mammography trained DCNN. 19,632 regions-of-interest (ROI) from 2,454 mass lesions were collected from two imaging modalities: digitized-screen film mammography (SFM) and full-field digital mammography (DM), and split into training and test sets. In the multi-task transfer learning, the DCNN learned the mass classification task simultaneously from the training set of SFM and DM. The best transfer network for mammography was selected from three transfer networks with different number of convolutional layers frozen. The performance of single-task and multitask transfer learning on an independent SFM test set in terms of the area under the receiver operating characteristic curve (AUC) was 0.78+/-0.02 and 0.82+/-0.02, respectively. In the second stage cross-domain transfer learning, a set of 12,680 ROIs from 317 mass lesions on DBT were split into validation and independent test sets. We first studied the data requirements for the first stage mammography trained DCNN by varying the mammography training data from 1% to 100% and evaluated its learning on the DBT validation set in inference mode. We found that the entire available mammography set provided the best generalization. The DBT validation set was then used to train only the last four fully connected layers, resulting in an AUC of 0.90+/-0.04 on the independent DBT test set.

The impact of training under different visual-spatial conditions on reverse-alignment laparoscopic skills development.

PubMed

Holznecht, Catherine; Schmidt, Travis; Gould, Jon

2012-01-01

Circumstances may arise during laparoscopic procedures in which alignment of the laparoscope and the instruments is off by 180°, creating a mirror image of the operative field. It has been shown that task performance is degraded under these reverse-alignment conditions, and that the magnitude of performance impairment is directly related to laparoscopic experience and skill. The aim of this study was to determine if reverse-alignment surgical skills could be developed through training. Twenty-two medical students were randomized to train in either reverse- or forward-alignment conditions on a standardized laparoscopic task in a video trainer (peg transfer). Baseline scores were attained for each group under both orientations. Subjects participated in three 1-h training sessions during an 8-week period. Post-training scores were then obtained under both alignment conditions. Pre and post-training scores were compared for users in each study group under both conditions. Post-training assessments in the forward orientation demonstrated that subjects in the forward-training group improved significantly compared to pre-testing, while the performance of subjects in the reverse-training group did not improve. Under reverse-alignment conditions, both groups improved on post-test assessment, with dramatic improvements observed for those in the reverse-training group. Laparoscopic novices can learn to adapt to a sensorimotor discordance in a simulated training environment. While it is possible that skills developed by training under standard forward-alignment conditions can be utilized in situations of extreme visual-spatial discordance, the intentional development of reverse-alignment skills by training under these conditions may prove beneficial to novice surgeons.

Comparative Performance in Single-Port Versus Multiport Minimally Invasive Surgery, and Small Versus Large Operative Working Spaces

PubMed Central

Marcus, Hani J.; Seneci, Carlo A.; Hughes-Hallett, Archie; Cundy, Thomas P.; Nandi, Dipankar; Yang, Guang-Zhong; Darzi, Ara

2015-01-01

Background. Surgical approaches such as transanal endoscopic microsurgery, which utilize small operative working spaces, and are necessarily single-port, are particularly demanding with standard instruments and have not been widely adopted. The aim of this study was to compare simultaneously surgical performance in single-port versus multiport approaches, and small versus large working spaces. Methods. Ten novice, 4 intermediate, and 1 expert surgeons were recruited from a university hospital. A preclinical randomized crossover study design was implemented, comparing performance under the following conditions: (1) multiport approach and large working space, (2) multiport approach and intermediate working space, (3) single-port approach and large working space, (4) single-port approach and intermediate working space, and (5) single-port approach and small working space. In each case, participants performed a peg transfer and pattern cutting tasks, and each task repetition was scored. Results. Intermediate and expert surgeons performed significantly better than novices in all conditions (P < .05). Performance in single-port surgery was significantly worse than multiport surgery (P < .01). In multiport surgery, there was a nonsignificant trend toward worsened performance in the intermediate versus large working space. In single-port surgery, there was a converse trend; performances in the intermediate and small working spaces were significantly better than in the large working space. Conclusions. Single-port approaches were significantly more technically challenging than multiport approaches, possibly reflecting loss of instrument triangulation. Surprisingly, in single-port approaches, in which triangulation was no longer a factor, performance in large working spaces was worse than in intermediate and small working spaces. PMID:26464468

Effect of PEG and mPEG-anthracene on tRNA aggregation and particle formation.

PubMed

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2012-01-09

Poly(ethylene glycol) (PEG) and its derivatives are synthetic polymers with major applications in gene and drug delivery systems. Synthetic polymers are also used to transport miRNA and siRNA in vitro. We studied the interaction of tRNA with several PEGs of different compositions, such as PEG 3350, PEG 6000, and mPEG-anthracene under physiological conditions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods as well as atomic force microscopy (AFM) were used to analyze the PEG binding mode, the binding constant, and the effects of polymer complexation on tRNA stability, aggregation, and particle formation. Structural analysis showed that PEG-tRNA interaction occurs via RNA bases and the backbone phosphate group with both hydrophilic and hydrophobic contacts. The overall binding constants of K(PEG 3350-tRNA)= 1.9 (±0.5) × 10(4) M(-1), K(PEG 6000-tRNA) = 8.9 (±1) × 10(4) M(-1), and K(mPEG-anthracene)= 1.2 (±0.40) × 10(3) M(-1) show stronger polymer-RNA complexation by PEG 6000 and by PEG 3350 than the mPEG-anthracene. AFM imaging showed that PEG complexes contain on average one tRNA with PEG 3350, five tRNA with PEG 6000, and ten tRNA molecules with mPEG-anthracene. tRNA aggregation and particle formation occurred at high polymer concentrations, whereas it remains in A-family structure.

Lesions of the rat nucleus basalis magnocellularis disrupt appetitive-to-aversive transfer learning.

PubMed

Butt, A E; Schultz, J A; Arnold, L L; Garman, E E; George, C L; Garraghty, P E

2003-01-01

Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.

Efficacy and tolerability of peg-only laxative on faecal impaction and chronic constipation in children. A controlled double blind randomized study vs a standard peg-electrolyte laxative

PubMed Central

2012-01-01

Background PEG-based laxatives are considered today the gold standard for the treatment of constipation in children. PEG formulations differ in terms of composition of inactive ingredients which may have an impact on acceptance, compliance and adherence to treatment. We therefore compared the efficacy, tolerability, acceptance and compliance of a new PEG-only formulation compared to a reference PEG-electrolyte (PEG-EL) formulation in resolving faecal impaction and in the treatment of chronic constipation. Methods Children aged 2–16 years with functional chronic constipation for at least 2 months were randomized to receive PEG-only 0.7 g/kg/day in 2 divided doses or 6.9 g PEG-EL 1–4 sachets according to age for 4 weeks. Children with faecal impaction were randomized to receive PEG-only 1.5/g/kg in 2 divided doses until resolution or for 6 days or PEG-EL with an initial dose of 4 sachets and increasing 2 sachets a day until resolution or for 7 days. Results Ninety-six children were randomized into the study. Five patients withdrew consent before starting treatment. Three children discontinued treatment for refusal due to bad taste of the product (1 PEG-only, 2 PEG-EL); 1 (PEG-EL) for an adverse effect (abdominal pain). Intent-to-treat analysis was carried out in 49 children in the PEG-only group and 42 in the PEG-EL group. No significant differences were observed between the two treatment groups at baseline. Adequate relief of constipation in terms of normalized frequency and painless defecation of soft stools was achieved in all patients in both groups. The number of stools/week was 9.2 ± 3.2 (mean ± SD) in the PEG-only group and 7.8 ± 2.4 in the PEG-EL group (p = 0.025); the number of days with stool was 22.4 ± 5.1 in the PEG-only group and 19.6 ± 7.2 in the PEG-EL group (p = 0.034). In the PEG-only group faecaloma resolution was observed in 5 children on the second day and in 2 children on the third day, while in the PEG-EL group it was observed in 2 children on the second day, in 3 children on the third day and in 1 child on the fifth day. Only 2 patients reported mild treatment-related adverse events: 1 child in the PEG-only group had diarrhoea and vomiting and 1 child in the PEG-EL group had abdominal pain requiring treatment discontinuation. The PEG-only preparation was better tolerated as shown by the lower frequency of nausea than in the PEG-EL group. In the PEG-only group, 96% of patients did not demonstrate any difficulties associated with treatment, as compared with 52% of patients in the PEG-EL group (p < 0.001). Also, the PEG-only formulation taste was better than that of PEG-EL (p < 0.001). The difference between the percentage of subjects who took > 80% of the prescribed dose was in favour of the PEG-only group (98% vs. 88%), though it did not reach a conventional statistical level (p = 0.062). Conclusion PEG-only was better tolerated and accepted than PEG-EL in children with chronic constipation. At the higher PEG doses recommended by the manufactures children in the PEG-only group had higher and more regular soft stool frequency than PEG-EL. Trial registration ClinicalTrials.gov: NCT01592734 PMID:23152962

Pharmacokinetic and Pharmacodynamic Properties of Calaspargase Pegol Escherichia coli L-Asparaginase in the Treatment of Patients With Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Study AALL07P4

PubMed Central

Angiolillo, Anne L.; Schore, Reuven J.; Devidas, Meenakshi; Borowitz, Michael J.; Carroll, Andrew J.; Gastier-Foster, Julie M.; Heerema, Nyla A.; Keilani, Taha; Lane, Ashley R.; Loh, Mignon L.; Reaman, Gregory H.; Adamson, Peter C.; Wood, Brent; Wood, Charlotte; Zheng, Hao W.; Raetz, Elizabeth A.; Winick, Naomi J.; Carroll, William L.; Hunger, Stephen P.

2014-01-01

Purpose Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL. Patients and Methods A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500. Results The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5× longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity ≥ 100 mIU/mL and ≥ 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups. Conclusion SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL. PMID:25348002

Critical determinant of intestinal permeability and oral bioavailability of pegylated all trans-retinoic acid prodrug-based nanomicelles: Chain length of poly (ethylene glycol) corona.

PubMed

Li, Zhenbao; Han, Xiaopeng; Zhai, Yinglei; Lian, He; Zhang, Dong; Zhang, Wenjuan; Wang, Yongjun; He, Zhonggui; Liu, Zheng; Sun, Jin

2015-06-01

Pegylation method is widely used to prolong the blood circulation time of proteins and nanoparticles after intravenous administration, but the effect of surface poly (ethylene glycol) (PEG) chain length on oral absorption of the pegylated nanoparticles is poorly reported. The aim of our study was to investigate the influence of PEG corona chain length on membrane permeability and oral bioavailability of the amphiphilic pegylated prodrug-based nanomicelles, taking all trans-retinoic acid (ATRA) as a model drug. The amphiphilic ATRA-PEG conjugates were synthesized by esterification reaction between all trans-retinoic acid and mPEGs (mPEG500, mPEG1000, mPEG2000, and mPEG5000). The conjugates could self-assemble in aqueous medium to form nanomicelles by emulsion-solvent evaporation method. The resultant nanomicelles were in spherical shape with an average diameter of 13-20 nm. The drug loading efficiency of ATRA-PEG500, ATRA-PEG1000, ATRA-PEG2000, and ATRA-PEG5000 was about 38.4, 26.6, 13.1, and 5.68 wt%, respectively. With PEG chain length ranging from 500 to 5000, ATRA-PEG nanomicelles exhibited a bell shape of chemical stability in different pH buffers, intestinal homogenate and plasma. More importantly, they were all rapidly hydrolyzed into the parent drug in hepatic homogenate, with the half-time values being 0.3-0.4h. In comparison to ATRA solution and ATRA prodrug-based nanomicelles, ATRA-PEG1000 showed the highest intestinal permeability. After oral administration, ATRA-PEG2000 and ATRA-PEG5000 nanomicelles were not nearly absorbed, while the oral bioavailability of ATRA-PEG500 and ATRA-PEG1000 demonstrated about 1.2- and 2.0-fold higher than ATRA solution. Our results indicated that PEG1000 chain length of ATRA-PEG prodrug nanomicelles has the optimal oral bioavailability probably due to improved stability and balanced mucus penetration capability and cell binding, and that the PEG chain length on a surface of nanoparticles cannot exceed a key threshold with the purpose of enhancement in oral bioavailability. Copyright © 2015. Published by Elsevier B.V.

Engineering vascularized soft tissue flaps in an animal model using human adipose–derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle

PubMed Central

Zhang, Qixu; Hubenak, Justin; Iyyanki, Tejaswi; Alred, Erik; Turza, Kristin C.; Davis, Greg; Chang, Edward I.; Branch-Brooks, Cynthia D.; Beahm, Elisabeth K.; Butler, Charles E.

2015-01-01

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold–stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model—hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber—provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects. PMID:26410787

Effect of the nanostructure and the surface composition of bimetallic Ni-Ru nanoparticles on the performance of CO methanation

NASA Astrophysics Data System (ADS)

Wang, Jing; Yuan, Changkun; Yao, Nan; Li, Xiaonian

2018-05-01

The Ni/SiO2 catalysts with trace Ru promoter were prepared by either polyethylene glycol (PEG)-assisted or PEG-free impregnation method and were used in CO methanation reaction. The presence of PEG molecules was beneficial to form bimetallic Ni-Ru particles with smaller size, better anti-sintering property and low-temperature reducibility on SiO2 support than the conventional PEG-free derived NiRu/SiO2 catalyst. Moreover, it was found that the low-temperature reduction at 573 K was favorable to form bimetallic Ni-Ru particles with more surface Ru atoms. This nanostructure not only allowed the electron transfer happening from Ru0 to Ni0 which led to its higher electron cloud density, but also could reduce the deposition of less reactive carbon on the catalyst. Therefore, the low-temperature reduction enhanced the reaction stability of NiRu/SiO2 catalyst. The increase of reduction temperature from 573 K to 693 K did not change the size of metallic particles, but decreased the amount of surface Ru atoms. It deactivated the catalyst due to the deposition of more less reactive carbon. Although the higher reduction temperature (e.g. 693 and 793 K) was unfavorable to the reaction stability, it created more surface defects. The amount of defects showed a volcano-shaped correlation with the reduction temperature which was consistent with the variation tendency of turnover frequency of CO conversion. Consequently, it evidenced that the amount of surface Ru atoms and defects on the bimetallic Ni-Ru particle played the critical roles on the stability and the intrinsic activity of methanation, respectively.

Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle.

PubMed

Zhang, Qixu; Hubenak, Justin; Iyyanki, Tejaswi; Alred, Erik; Turza, Kristin C; Davis, Greg; Chang, Edward I; Branch-Brooks, Cynthia D; Beahm, Elisabeth K; Butler, Charles E

2015-12-01

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold-stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model-hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber-provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation, characterization, and in vitro activity evaluation of triblock copolymer-based polymersomes for drugs delivery

NASA Astrophysics Data System (ADS)

Besada, Lucas N.; Peruzzo, Pablo; Cortizo, Ana M.; Cortizo, M. Susana

2018-03-01

Polymersomes are polymer-based vesicles that form upon hydration of amphiphilic block copolymers and display high stability and durability, due to their mechanical and physical properties. They have hydrophilic reservoirs as well as thick hydrophobic membranes; allowing to encapsulate both water-soluble bioactive agent and hydrophobic drugs. In this study, poly ethylene glycol (PEG3350 and PEG6000) were used as hydrophilic part and poly(vinyl benzoate) (PVBz) as hydrophobic block to synthesize amphiphilic triblock copolymers (PVBz- b-PEG- b-PVBz). Different proportions of hydrophilic/hydrophobic part were assayed in order to obtain polymersomes by solvent injection method. For the synthesis of the copolymers, the initial block of PEG was derived to obtain a macroinitiator through a xanthate functional group (PEGX3 or PEGX6) and the polymerization of vinyl benzoate was carried out through reversible addition-fragmentation chain transfer polymerization (RAFT). The structure of PEGX and copolymers was confirmed by Infrared, 1H-NMR and UV-Vis spectrometry, while the average molecular weight (Mw) and polydispersity index (PI) were determined by size exclusion chromatography (SEC). The structures adopted by the copolymers in aqueous solution by self-assembly were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Both techniques confirm that polymersomes were obtained for a fraction of hydrophilic block ( f) ≈ 35 ± 10%, with a diameter of 38.3 ± 0.3 nm or 22.5 ± 0.7 nm, as determined by TEM and according to the M w of the precursor block copolymer. In addition, we analyzed the possible cytotoxicity in view of its potential application as biomedical nanocarrier. The results suggest that polymersomes seem not induce cytotoxicity during the periods of time tested.

Biomaterials for the Decorporation of Sr-85 in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Creim, Jeffrey A.; Curry, Terry L.

2010-09-01

Although four stable isotopes of strontium occur naturally, strontium-90 is produced by nuclear fission and is present in surface soil around the world as a result of fallout from atmospheric nuclear weapons tests. It can easily transfer to man in the event of a nuclear/radiological emergency or through the plant-animal-human food chain causing long-term exposures. Strontium is chemically and biologically similar to calcium, and is incorporated primarily into bone following internal deposition. Alginic acid (alginate) obtained from seaweed (kelp) extract selectively binds ingested strontium in the GI tract blocking its systemic uptake and reducing distribution to bone in rats, whilemore » other natural polysaccharides including chitosan and hyaluronic acid had little in vivo affinity for strontium. Alginate exhibits the unique ability to discriminate between strontium and calcium and has been previously shown to reduce intestinal absorption and skeletal retention of strontium without changing calcium metabolism. In our studies, the effect of commercially available alginate on strontium intestinal absorption was examined. One problem associated with alginate treatment is its limited solubility and gel formation in water. The aqueous solubility of sodium alginate was improved in a sodium chloride/sodium bicarbonate electrolyte solution containing low molecular weight polyethylene glycol (PEG). Furthermore, oral administration of the combined alginate/electrolyte//PEG solution synergistically accelerated removal of internal strontium in rats when compared to treatment with individual sodium alginate/electrolyte or electrolyte/PEG solutions. Importantly, both alginate and PEG are nontoxic, readily available materials that can be easily administered orally in case of a national emergency when potentially large numbers of the population may require medical treatment for internal depositions. Our results suggest further studies to optimize in vivo decorporation performance of engineered alginate material via modification of its chemical and physicochemical properties is warranted.« less

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors

PubMed Central

Mastorakos, Panagiotis; Zhang, Clark; Song, Eric; Kim, Young Eun; Park, Hee Won; Berry, Sneha; Choi, Won Kyu; Hanes, Justin; Suk, Jung Soo

2018-01-01

The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5 kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain. PMID:28694032

Transfer of task-switching training in older age: the role of verbal processes.

PubMed

Karbach, Julia; Mang, Sandra; Kray, Jutta

2010-09-01

This study investigated the influence of verbal self-instructions (VSI) on the transfer of task-switching training in older adults (56-78 years). We applied an internally cued switching paradigm in a pretest-training-posttest design. Training-related improvements were not modulated by VSI. Transfer (the pretest-posttest reduction of switch costs) was most pronounced when participants applied the VSI at posttest after practicing the switching task without VSI. The results indicate that in contrast to transfer of executive control training, transfer of (verbal) strategy training seems to be limited and that VSI is most beneficial when the task-switching abilities are already well practiced. (c) 2010 APA, all rights reserved.

Performing a reaching task with one arm while adapting to a visuomotor rotation with the other can lead to complete transfer of motor learning across the arms

PubMed Central

Lei, Yuming; Binder, Jeffrey R.

2015-01-01

The extent to which motor learning is generalized across the limbs is typically very limited. Here, we investigated how two motor learning hypotheses could be used to enhance the extent of interlimb transfer. According to one hypothesis, we predicted that reinforcement of successful actions by providing binary error feedback regarding task success or failure, in addition to terminal error feedback, during initial training would increase the extent of interlimb transfer following visuomotor adaptation (experiment 1). According to the other hypothesis, we predicted that performing a reaching task repeatedly with one arm without providing performance feedback (which prevented learning the task with this arm), while concurrently adapting to a visuomotor rotation with the other arm, would increase the extent of transfer (experiment 2). Results indicate that providing binary error feedback, compared with continuous visual feedback that provided movement direction and amplitude information, had no influence on the extent of transfer. In contrast, repeatedly performing (but not learning) a specific task with one arm while visuomotor adaptation occurred with the other arm led to nearly complete transfer. This suggests that the absence of motor instances associated with specific effectors and task conditions is the major reason for limited interlimb transfer and that reinforcement of successful actions during initial training is not beneficial for interlimb transfer. These findings indicate crucial contributions of effector- and task-specific motor instances, which are thought to underlie (a type of) model-free learning, to optimal motor learning and interlimb transfer. PMID:25632082

A Polyamine Oxidizing Enzyme as a Drug to Treat Breast Cancer

DTIC Science & Technology

2007-07-01

is a viable anticancer therapy. BODY TASK 1. Prepare enough of two polyethylene glycol(PEG)-derivatives of bovine serum amine oxidase (SAO...interfere with its PEGylation and/or obscure the outcome of experiments to test the treatment as an anticancer therapy. Hence, another few weeks were...attached polysaccharide , thus, minimize interference with or mimicking of the mouse’s own SAO. A small amount of bovine SAO was PEGylated at pH 7.4 with

Crystalline polyoxometalate (POM)–polyethylene glycol (PEG) composites aimed as non-humidified intermediate-temperature proton conductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuboi, Masaki; Hibino, Mitsuhiro; Mizuno, Noritaka

2016-02-15

Crystalline polyoxometalate (POM)–polyethylene glycol (PEG) composites aimed as non-humidified intermediate-temperature proton conductors were synthesized and characterized by single crystal and powder XRD, solid state MASNMR, and TG-DTA measurements. Among the POM–PEG composites, Cs{sub 2.7}H{sub 0.3}[PW{sub 12}O{sub 40}]·1.2PEG1000 (CsHPW-PEG1000) possessed one-dimensional channels with diameters of ca. 6 and 8 Å, where PEG probably resided, and showed the best performance as a proton conductor (1.2×10{sup −5} S cm{sup −1} at 443 K). Proton conductivities of POM–PEG composites decreased by the increase in molecular weights of PEG (CsHPW-PEG12,000) or anion charges (CsHSiW-PEG1000). Variable contact time {sup 13}C-CP (cross polarization) MASNMR revealed that localmore » mobility (i.e., segmental motion) of PEG is related to the trends in proton conductivities. These results show that amount of acidic protons (H{sup +}) is not the primary factor in proton conduction and that segmental motion of PEG assists the proton hopping among POMs in the crystal lattice of POM–PEG composites. - Graphical abstract: Non-humidified intermediate-temperature proton conduction in crystalline polyoxometalate (POM)–polyethylene (PEG) composites are assisted by the segmental motion of PEG. - Highlights: • Crystalline polyoxometalate–polyethlene glycol (PEG) composites were synthesized. • CsHPW-PEG1000 possessed one-dimensional channels and showed the highest proton conductivity. • {sup 13}C CPMASNMR revealed that segmental motion of PEG is related to the proton conduction.« less

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interdisciplinary rehabilitation for a patient with incomplete cervical spinal cord injury and multimorbidity

PubMed Central

Vining, Robert D.; Gosselin, Donna M.; Thurmond, Jeb; Case, Kimberlee; Bruch, Frederick R.

2017-01-01

Abstract Rationale: This report describes interdisciplinary rehabilitation for a 51-year-old male recovering from incomplete cervical spinal cord injury (SCI) and multiple comorbidities following an automobile accident. Patient concerns: The patient was admitted to a rehabilitation specialty hospital approximately 2 months post SCI and 2 separate surgical fusion procedures (C3–C6). Diagnoses: Clinical presentation at the rehabilitation hospital included moderate to severe motor strength loss in both upper and lower extremities, a percutaneous endoscopic gastronomy tube (PEG), dysphagia, bowel/bladder incontinence, dependence on a mechanical lift and tilting wheelchair due to severe orthostatic hypotension, and pre-existing shoulder pain from bilateral joint degeneration. Interventions: The interdisciplinary team formally coordinated rehabilitative care from multiple disciplines. Internal medicine managed medications, determined PEG removal, monitored co-morbid conditions, and overall progress. Chiropractic care focused on alleviating shoulder and thoracic pain and improving spinal and extremity mobility. Physical therapy addressed upright tolerance, transfer, gait, and strength training. Occupational therapy focused on hand coordination and feeding/dressing activities. Psychology assisted with coping strategies. Nursing ensured medication adherence, nutrient intake, wound prevention, and incontinence management, whereas physiatry addressed abnormal muscle tone. Outcomes: Eleven months post-admission the patient's progress allowed discharge to a long-term care facility. At this time he was without dysphagia or need for a PEG. Orthostatic hypotension and bilateral shoulder pain symptoms were also resolved while bowel/bladder incontinence and upper and lower extremity motor strength loss remained. He was largely independent in transferring from bed to wheelchair and in upper body dressing. Lower body dressing/bathing required maximal assistance. Gait with a 2-wheeled walker was possible up to 150 feet with verbal cues and occasional stabilizing assistance. Lessons: Several specialties functioning within an interdisciplinary team fulfilled complementary roles to support rehabilitation for a patient with SCI. PMID:28834891

Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use

PubMed Central

Shin, Chan Young; Kim, Kyu-Bong

2015-01-01

Polyethylene glycols (PEGs) are products of condensed ethylene oxide and water that can have various derivatives and functions. Since many PEG types are hydrophilic, they are favorably used as penetration enhancers, especially in topical dermatological preparations. PEGs, together with their typically nonionic derivatives, are broadly utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners. The compounds studied in this review include PEG/PPG-17/6 copolymer, PEG-20 glyceryl triisostearate, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil. Overall, much of the data available in this review are on PEGylated oils (PEG-40 and PEG-60 hydrogenated castor oils), which were recommended as safe for use in cosmetics up to 100% concentration. Currently, PEG-20 glyceryl triisostearate and PEGylated oils are considered safe for cosmetic use according to the results of relevant studies. Additionally, PEG/PPG-17/6 copolymer should be further studied to ensure its safety as a cosmetic ingredient. PMID:26191379

Avidin-biotin-PEG-CPA complexes as potential EPR-directed therapeutic protein carriers: preparation and characterization.

PubMed

Ke, Shan; Wright, John C; Kwon, Glen S

2007-01-01

Bovine carboxypeptidase A (CPA) conjugated with biotinylated poly(ethylene glycol) (PEG) has been synthesized and characterized in terms of stoichiometry and half-life of the avidin-biotin-PEG(s)-CPA complex. The half-lives for dissociation are 3.34 days for the avidin-biotin-PEG(3400)-CPA 1:1 complex, 3.65 days for the avidin-biotin-PEG(5000)-CPA 1:1 complex, 3.91 days for the avidin-biotin-PEG(3400)-CPA-PEG(2000) 1:1 complex, and 2.74 days for the avidin-biotin-PEG(5000)-CPA-PEG(2000) 1:1 complex. The slow dissociation demonstrates the stability of complexes using a PEGylated biotin terminus as a linker with avidin. The stoichiometry of the biotin-PEGylated CPA with avidin was determined by the 2,6-ANS method, and the results are consistent with measurements of the stoichiometry using size exclusion chromatography. The stoichiometries are 1:2 for the avidin-biotin-PEG(3400)-CPA complex and the avidin-biotin-PEG(3400)-CPA-PEG(2000) complex, 1:1 for the avidin-biotin-PEG(5000)-CPA complex, and 1:4 for the avidin-biotin-PEG(5000)-CPA-PEG(2000) complex. These findings stress both the importance of the length of a PEG chain as an appropriate spacer between the biotin terminus and a functional group, and the great potential of the avidin-biotin-PEGylated-protein complex as a therapeutic protein delivery system for solid tumor prodrug targeting.

Preparation of Polyamide-6 Submicrometer-Sized Spheres by In Situ Polymerization.

PubMed

Zhao, Xingke; Xia, Housheng; Fu, Xubing; Duan, Jianping; Yang, Guisheng

2015-11-01

Polyamide-6 (PA6) submicron-sized spheres are prepared by two steps: (1) anionic ring-opening polymerization of ε-caprolactam in the presence of poly(ethylene glycol)-block-poly-(propylene glycol)-block-poly(ethylene glycol)(PEG-b-PPG-b-PEG) and (2) separation of PA6 spheres by dissolving PEG-b-PPG-b-PEG from the prepared blends. The PA6 microspheres obtained are regular spherical, with diameter ranging from 200 nm to 2 μm and narrow size distribution, as confirmed by scanning electron microscopy. By comparison with PA6/PS and PA6/PEG systems, it is denominated that the PEG blocks in PEG-b-PPG-b-PEG can effectively reduce the surface tension of PA6 droplets and further decrease the diameter of the PA6 microspheres. The PPG block in PEG-b-PPG-b-PEG can prevent the PA6 droplets coalescing with each other, and isolated spherical particles can be obtained finally. The phase inversion of the PA6/PEG-b-PPG-b-PEG blends occurs at very low PEG-b-PPG-b-PEG content; the PEG-b-PPG-b-PEG phase can be removed by water easily. The whole experiment can be finished in a short time (approximately in half an hour) without using any organic solvents; it is an efficient strategy for the preparation of submicron-sized PA6 microspheres. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multisensory perceptual learning of temporal order: audiovisual learning transfers to vision but not audition.

PubMed

Alais, David; Cass, John

2010-06-23

An outstanding question in sensory neuroscience is whether the perceived timing of events is mediated by a central supra-modal timing mechanism, or multiple modality-specific systems. We use a perceptual learning paradigm to address this question. Three groups were trained daily for 10 sessions on an auditory, a visual or a combined audiovisual temporal order judgment (TOJ). Groups were pre-tested on a range TOJ tasks within and between their group modality prior to learning so that transfer of any learning from the trained task could be measured by post-testing other tasks. Robust TOJ learning (reduced temporal order discrimination thresholds) occurred for all groups, although auditory learning (dichotic 500/2000 Hz tones) was slightly weaker than visual learning (lateralised grating patches). Crossmodal TOJs also displayed robust learning. Post-testing revealed that improvements in temporal resolution acquired during visual learning transferred within modality to other retinotopic locations and orientations, but not to auditory or crossmodal tasks. Auditory learning did not transfer to visual or crossmodal tasks, and neither did it transfer within audition to another frequency pair. In an interesting asymmetry, crossmodal learning transferred to all visual tasks but not to auditory tasks. Finally, in all conditions, learning to make TOJs for stimulus onsets did not transfer at all to discriminating temporal offsets. These data present a complex picture of timing processes. The lack of transfer between unimodal groups indicates no central supramodal timing process for this task; however, the audiovisual-to-visual transfer cannot be explained without some form of sensory interaction. We propose that auditory learning occurred in frequency-tuned processes in the periphery, precluding interactions with more central visual and audiovisual timing processes. Functionally the patterns of featural transfer suggest that perceptual learning of temporal order may be optimised to object-centered rather than viewer-centered constraints.

TRAQUEOESOPHAGEAL FISTULA PATIENTS FED THROUGH PERCUTANEOUS ENDOSCOPIC GASTROSTOMY/GASTROJEJUNOSTOMY: NUTRITIONAL STATUS AND CLINICAL OUTCOME.

PubMed

Santos, Carla Adriana; Pereira, Marta; Martins, Vera Santos; Fonseca, Jorge

2015-08-01

tracheoesophageal fistula (TEF) may result from cancer or mechanical ventilation. Endoscopic Gastrostomy or Gastrojejunostomy (PEG/PEG-J) is used for nutritional support. in TEF-patients, evaluating nutritional status when PEG is performed, safety of PEG/PEG-J and clinical outcome. from the files of PEG/PEG-J feed TEF-patients we collected: clinical data, Body Mass Index, albumin, transferrin and cholesterol when gastrostomy was performed, and clinical outcome globally and according with the TEF cause: Group 1: complication of mechanical ventilation, Group 2: cancer. twelve patients, 18-91 years (median: 53), 11 PEG, one PEG-J: six complications of ventilation (neurological diseases), 6 cancers. Mean period from TEF diagnosis until gastrostomy: 2 months in Group 1, 10 months in Group 2. In the day of the gastrostomy, patients presented with malnutrition parameters, most strikingly in the cancer group. Group 1: died a single patient, 3 closed the TEF, resuming oral intake, 2 are still PEG-feed. All cancer patients died (7 months after gastrostomy). One needed a jejunal extension to create a PEG-J. No more complications. PEG/PEG-J was safe in TEF-patients, but cancer patients underwent gastrostomy too late. In TEF-patients, PEG/PEG-J should be considered in a regular basis, earlier in the disease evolution, before established malnutrition. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Chemiluminescence Resonance Energy Transfer Competitive Immunoassay Employing Hapten-Functionalized Quantum Dots for the Detection of Sulfamethazine.

PubMed

Ma, Mingfang; Wen, Kai; Beier, Ross C; Eremin, Sergei A; Li, Chenglong; Zhang, Suxia; Shen, Jianzhong; Wang, Zhanhui

2016-07-20

We describe a new strategy for using chemiluminescence resonance energy transfer (CRET) by employing hapten-functionalized quantum dots (QDs) in a competitive immunoassay for detection of sulfamethazine (SMZ). Core/multishell QDs were synthesized and modified with phospholipid-PEG. The modified QDs were functionalized with the hapten 4-(4-aminophenyl-sulfonamido)butanoic acid. The CRET-based immunoassay exhibited a limit of detection for SMZ of 9 pg mL(-1), which is >4 orders of magnitude better than a homogeneous fluorescence polarization immunoassay and is 2 orders of magnitude better than a heterogeneous enzyme-linked immunosorbent assay. This strategy represents a simple, reliable, and universal approach for detection of chemical contaminants.

Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake

NASA Astrophysics Data System (ADS)

Rao, Lang; Xu, Jun-Hua; Cai, Bo; Liu, Huiqin; Li, Ming; Jia, Yan; Xiao, Liang; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

2016-02-01

Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle ‘stealth’. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications.

The importance of training strategy adaptation: a learner-oriented approach for improving older adults' memory and transfer.

PubMed

Bottiroli, Sara; Cavallini, Elena; Dunlosky, John; Vecchi, Tomaso; Hertzog, Christopher

2013-09-01

We investigated the benefits of strategy-adaptation training for promoting transfer effects. This learner-oriented approach--which directly encourages the learner to generalize strategic behavior to new tasks--helps older adults appraise new tasks and adapt trained strategies to them. In Experiment 1, older adults in a strategy-adaptation training group used 2 strategies (imagery and sentence generation) while practicing 2 tasks (list and associative learning); they were then instructed on how to do a simple task analysis to help them adapt the trained strategies for 2 different unpracticed tasks (place learning and text learning) that were discussed during training. Two additional criterion tasks (name-face associative learning and grocery-list learning) were never mentioned during training. Two other groups were included: A strategy training group (who received strategy training and transfer instructions but not strategy-adaptation training) and a waiting-list control group. Both training procedures enhanced older adults' performance on the trained tasks and those tasks that were discussed during training, but transfer was greatest after strategy-adaptation training. Experiment 2 found that strategy-adaptation training conducted via a manual that older adults used at home also promoted transfer. These findings demonstrate the importance of adopting a learner-oriented approach to promote transfer of strategy training. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Training attentional control in older adults.

PubMed

Mackay-Brandt, Anna

2011-07-01

Recent research has demonstrated benefits for older adults from training attentional control using a variable priority strategy, but the construct validity of the training task and the degree to which benefits of training transfer to other contexts are unclear. The goal of this study was to characterize baseline performance on the training task in a sample of 105 healthy older adults and to test for transfer of training in a subset (n = 21). Training gains after 5 days and extent of transfer was compared to another subset (n = 20) that served as a control group. Baseline performance on the training task was characterized by a two-factor model of working memory and processing speed. Processing speed correlated with the training task. Training gains in speed and accuracy were reliable and robust (ps <.001, η(2) = .57 to .90). Transfer to an analogous task was observed (ps <.05, η(2) = .10 to .17). The beneficial effect of training did not translate to improved performance on related measures of processing speed. This study highlights the robust effect of training and transfer to a similar context using a variable priority training task. Although processing speed is an important aspect of the training task, training benefit is either related to an untested aspect of the training task or transfer of training is limited to the training context.

Application of microchip CGE for the analysis of PEG-modified recombinant human granulocyte-colony stimulating factors.

PubMed

Park, Eun Ji; Lee, Kyung Soo; Lee, Kang Choon; Na, Dong Hee

2010-11-01

The purpose of this study was to evaluate the microchip CGE (MCGE) for the analysis of PEG-modified granulocyte-colony stimulating factor (PEG-G-CSF) prepared with PEG-aldehydes. The unmodified and PEG-modified G-CSFs were analyzed by Protein 80 and 230 Labchips on the Agilent 2100 Bioanalyzer. The MCGE allowed size-based separation and quantitation of PEG-G-CSF. The Protein 80 Labchip was useful for PEG-5K-G-CSF, while the Protein 230 Labchip was more suitable for PEG-20K-G-CSF. The MCGE was also used to monitor a search for optimal PEG-modification (PEGylation) conditions to produce mono-PEG-G-CSF. This study demonstrates the usefulness of MCGE for monitoring and optimizing the PEGylation of G-CSF with the advantages of speed, minimal sample consumption, and automatic quantitation.

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy.

PubMed

Valiante, Flavio; Bellumat, Angelo; De Bona, Manuela; De Boni, Michele

2013-09-07

To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy.

The quest for biocompatible phthalocyanines for molecular imaging: Photophysics, relaxometry and cytotoxicity studies.

PubMed

Pinto, Sara M A; Tomé, Vanessa A; Calvete, Mário J F; Pereira, Mariette M; Burrows, Hugh D; Cardoso, Ana M S; Pallier, Agnès; C A Castro, M Margarida; Tóth, Éva; Geraldes, Carlos F G C

2016-01-01

Water soluble phthalocyanines bearing either four PEG500 or four choline substituents in the macrocyclic structure, as well as their Zn(II) and Mn(III) complexes were synthesized. The metal-free and Zn(II) complexes present relatively high fluorescence quantum yields (up to 0.30), while the Mn(III) complexes show no fluorescence as a consequence of rapid non-radiative deactivation of the Mn(III) phthalocyanine excited states through low-lying metal based or charge-transfer states. The effect of DMSO on the aggregation of the phthalocyanines was studied. It was not possible to obtain the Mn(II) complexes by reduction of the corresponding Mn(III) complexes due to the presence of electron donating substituents at the periphery of the phthalocyanines. The (1)H NMRD plots of the PEG500 and choline substituted Mn(III)-phthalocyanine complexes are typical of self-aggregated Mn(III) systems with r1 relaxivities of 4.0 and 5.7mM(-1)s(-1) at 20MHz and 25°C. The Mn(III)-phthalocyanine-PEG4 complex shows no significant cytotoxicity to HeLa cell cultures after 2h of incubation up to 2mM concentration. After 24h of cell exposure to the compound, significant toxicity was observed for all the concentrations tested with IC50 of 1.105mM. Copyright © 2015 Elsevier Inc. All rights reserved.

Dehydration-Induced Redistribution of Amphiphilic Molecules between Cytoplasm and Lipids Is Associated with Desiccation Tolerance in Seeds1

PubMed Central

Buitink, Julia; Leprince, Olivier; Hoekstra, Folkert A.

2000-01-01

This study establishes a relationship between desiccation tolerance and the transfer of amphiphilic molecules from the cytoplasm into lipids during drying, using electron paramagnetic resonance spectroscopy of amphiphilic spin probes introduced into imbibed radicles of pea (Pisum sativum) and cucumber (Cucumis sativa) seeds. Survival following drying and a membrane integrity assay indicated that desiccation tolerance was present during early imbibition and lost in germinated radicles. In germinated cucumber radicles, desiccation tolerance could be re-induced by an incubation in polyethylene glycol (PEG) before drying. In desiccation-intolerant radicles, partitioning of spin probes into lipids during dehydration occurred at higher water contents compared with tolerant and PEG-induced tolerant radicles. The difference in partitioning behavior between desiccation-tolerant and -intolerant tissues could not be explained by the loss of water. Consequently, using a two-phase model system composed of sunflower or cucumber oil and water, physical properties of the aqueous solvent that may affect the partitioning of amphiphilic spin probes were investigated. A significant relationship was found between the partitioning of spin probes and the viscosity of the aqueous solvent. Moreover, in desiccation-sensitive radicles, the rise in cellular microviscosity during drying commenced at higher water contents compared with tolerant or PEG-induced tolerant radicles, suggesting that the microviscosity of the cytoplasm may control the partitioning behavior in dehydrating seeds. PMID:11080316

The Relationship between N-Back Performance and Matrix Reasoning--Implications for Training and Transfer

ERIC Educational Resources Information Center

Jaeggi, Susanne M.; Studer-Luethi, Barbara; Buschkuehl, Martin; Su, Yi-Fen; Jonides, John; Perrig, Walter J.

2010-01-01

We have previously demonstrated that training on a dual n-back task results in improvements in fluid intelligence ("Gf") as measured by matrix reasoning tasks. Here, we explored the underlying mechanisms of this transfer effect in two studies, and we evaluated the transfer potential of a single n-back task. In the first study, we demonstrated that…

Speech responses and dual-task performance - Better time-sharing or asymmetric transfer?

NASA Technical Reports Server (NTRS)

Vidulich, Michael A.

1988-01-01

The value of speech controls in a dual-task experiment that also evaluated asymmetric transfer effects is considered. There was no evidence of asymmetric transfer in spite of significant effects supporting the advantage of mixing manual and speech responses. The data suggest that speech controls can be used to enhance performance in operational multiple-task environments.

Stable Nuclear Transformation System for the Coccolithophorid Alga Pleurochrysis carterae

PubMed Central

Endo, Hirotoshi; Yoshida, Megumi; Uji, Toshiki; Saga, Naotsune; Inoue, Koji; Nagasawa, Hiromichi

2016-01-01

Of the three dominant marine microalgal groups, dinoflagellates and diatoms can undergo genetic transformation; however, no transformation method has been established for haptophytes to date. Here, we report the first stable genetic transformation of a coccolithophore, Pleurochrysis carterae, by means of polyethylene glycol (PEG)-mediated transfer of a bacterial hygromycin B-resistance gene. Together with the novel transient green fluorescent protein (GFP) expression system, this approach should facilitate further molecular-based research in this phylum. PMID:26947136

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

PubMed

Liu, Jian; Ohta, Shin-Ichi; Sonoda, Akinaga; Yamada, Masatoshi; Yamamoto, Masaya; Nitta, Norihisa; Murata, Kiyoshi; Tabata, Yasuhiko

2007-01-22

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Cognitive and Physical Fatigue Tasks Enhance Pain, Cognitive Fatigue and Physical Fatigue in People with Fibromyalgia

PubMed Central

Dailey, Dana L; Keffala, Valerie J; Sluka, Kathleen A

2014-01-01

Objective Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue. The primary objective of this study was to determine if pain, perceived cognitive fatigue, and perceived physical fatigue were enhanced in participants with fibromyalgia compared to healthy controls during a cognitive fatigue task, a physical fatigue task and a dual fatigue task. Methods Twenty four people with fibromyalgia and 33 healthy controls completed pain, fatigue and function measures. A cognitive fatigue task (Controlled Oral Word Association Test) and physical fatigue task (Valpar peg test) were done individually and combined for a dual fatigue task. Resting pain, perceived cognitive fatigue and perceived physical fatigue were assessed during each task using visual analogue scales. Function was assessed with shoulder range of motion and grip. Results People with fibromyalgia had significantly higher increases in pain, cognitive fatigue and physical fatigue when compared to healthy controls after completion of a cognitive fatigue task, a physical fatigue task, or a dual fatigue task (p<0.01). People with fibromyalgia performed equivalently on measures of physical performance and cognitive performance on the physical and cognitive fatigue tasks, respectively. Conclusions These data show that people with fibromyalgia show larger increases in pain, perceived cognitive fatigue and perceived physical fatigue to both cognitive and physical fatigue tasks compared to healthy controls. The increases in pain and fatigue during cognitive and physical fatigue tasks could influence subject participation in daily activities and rehabilitation. PMID:25074583

Training specificity and transfer in time and distance estimation.

PubMed

Healy, Alice F; Tack, Lindsay Anderson; Schneider, Vivian I; Barshi, Immanuel

2015-07-01

Learning is often specific to the conditions of training, making it important to identify which aspects of the testing environment are crucial to be matched in the training environment. In the present study, we examined training specificity in time and distance estimation tasks that differed only in the focus of processing (FOP). External spatial cues were provided for the distance estimation task and for the time estimation task in one condition, but not in another. The presence of a concurrent alphabet secondary task was manipulated during training and testing in all estimation conditions in Experiment 1. For distance as well as for time estimation in both conditions, training of the primary estimation task was found to be specific to the presence of the secondary task. In Experiments 2 and 3, we examined transfer between one estimation task and another, with no secondary task in either case. When all conditions were equal aside from the FOP instructions, including the presence of external spatial cues, Experiment 2 showed "transfer" between tasks, suggesting that training might not be specific to the FOP. When the external spatial cues were removed from the time estimation task, Experiment 3 showed no transfer between time and distance estimations, suggesting that external task cues influenced the procedures used in the estimation tasks.

Rootstock alleviates PEG-induced water stress in grafted pepper seedlings: physiological responses.

PubMed

Penella, Consuelo; Nebauer, Sergio G; Bautista, Alberto San; López-Galarza, Salvador; Calatayud, Ángeles

2014-06-15

Recent studies have shown that tolerance to abiotic stress, including water stress, is improved by grafting. In a previous work, we took advantage of the natural variability of Capsicum spp. and selected accessions tolerant and sensitive to water stress as rootstocks. The behavior of commercial cultivar 'Verset' seedlings grafted onto the selected rootstocks at two levels of water stress provoked by adding 3.5 and 7% PEG (polyethylene glycol) was examined over 14 days. The objective was to identify the physiological traits responsible for the tolerance provided by the rootstock in order to determine if the tolerance is based on the maintenance of the water relations under water stress or through the activation of protective mechanisms. To achieve this goal, various physiological parameters were measured, including: water relations; proline accumulation; gas exchange; chlorophyll fluorescence; nitrate reductase activity; and antioxidant capacity. Our results indicate that the effect of water stress on the measured parameters depends on the duration and intensity of the stress level, as well as the rootstock used. Under control conditions (0% PEG) all plant combinations showed similar values for all measured parameters. In general terms, PEG provoked a strong decrease in the gas exchange parameters in the cultivar grafted onto the sensitive accessions, as also observed in the ungrafted plants. This effect was related to lower relative water content in the plants, provoked by an inefficient osmotic adjustment that was dependent on reduced proline accumulation. At the end of the experiment, chronic photoinhibition was observed in these plants. However, the plants grafted onto the tolerant rootstocks, despite the reduction in photosynthetic rate, maintained the protective capacity of the photosynthetic machinery mediated by osmotic adjustment (based on higher proline content). In addition, water stress limited uptake and further NO3(-) transfer to the leaves. Increased nitrate reductase activity in the roots was observed, mainly in plants grafted onto the sensitive rootstocks, as well as the ungrafted plants, and this was associated with the lessened flux to the leaves. This study suggests that PEG-induced water stress can be partially alleviated by using tolerant accessions as rootstocks. Copyright © 2014 Elsevier GmbH. All rights reserved.

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate).

PubMed

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO(3)H(2)) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y(2)O(3) nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO(3)H(2) (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO(3)H(2) was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.

Analysis of peg formation in cucumber seedlings grown on clinostats and in a microgravity (space) environment.

PubMed

Link, B M; Cosgrove, D J

1999-12-01

In young cucumber seedlings, the peg is a polar out-growth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. Previous studies have indicated that peg formation is gravity dependent. In this study we analyzed peg formation in cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) grown under conditions of normal gravity, microgravity, and simulated microgravity (clinostat rotation). Seeds were germinated on the ground, in clinostats and on board the space shuttle (STS 95) for 1-2 days, frozen and subsequently examined for their stage of development, degree of hook formation, number of pegs formed, and peg morphology. The frequency of peg formation in space grown seedlings was found to be nearly identical to that of clinostat grown seedlings and to differ from that of seedlings germinated under normal gravity only in a minority of cases; approximately 6% of the seedlings formed two pegs and nearly 2% of the seedlings lacked pegs, whereas such abnormalities did not occur in ground controls. The degree of hook formation was found to be less pronounced for space grown seedlings, compared to clinostat grown seedlings, indicating a greater degree of decoupling between peg formation and hook formation in space. Nonetheless, in all seedlings having single pegs and a hook, the peg was found to be positioned correctly on the inside of the hook, showing that there is coordinate development even in microgravity environments. Peg morphologies were altered in space grown samples, with the pegs having a blunt appearance and many pegs showing alterations in expansion, with the peg extending out over the edges of the seed coat and downwards. These phenotypes were not observed in clinostat or ground grown seedlings.

Analysis of peg formation in cucumber seedlings grown on clinostats and in a microgravity (space) environment

NASA Technical Reports Server (NTRS)

Link, B. M.; Cosgrove, D. J.

1999-01-01

In young cucumber seedlings, the peg is a polar out-growth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. Previous studies have indicated that peg formation is gravity dependent. In this study we analyzed peg formation in cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) grown under conditions of normal gravity, microgravity, and simulated microgravity (clinostat rotation). Seeds were germinated on the ground, in clinostats and on board the space shuttle (STS 95) for 1-2 days, frozen and subsequently examined for their stage of development, degree of hook formation, number of pegs formed, and peg morphology. The frequency of peg formation in space grown seedlings was found to be nearly identical to that of clinostat grown seedlings and to differ from that of seedlings germinated under normal gravity only in a minority of cases; approximately 6% of the seedlings formed two pegs and nearly 2% of the seedlings lacked pegs, whereas such abnormalities did not occur in ground controls. The degree of hook formation was found to be less pronounced for space grown seedlings, compared to clinostat grown seedlings, indicating a greater degree of decoupling between peg formation and hook formation in space. Nonetheless, in all seedlings having single pegs and a hook, the peg was found to be positioned correctly on the inside of the hook, showing that there is coordinate development even in microgravity environments. Peg morphologies were altered in space grown samples, with the pegs having a blunt appearance and many pegs showing alterations in expansion, with the peg extending out over the edges of the seed coat and downwards. These phenotypes were not observed in clinostat or ground grown seedlings.

Post-modification of preformed liposomes with novel non-phospholipid poly(ethylene glycol)-conjugated hexadecylcarbamoylmethyl hexadecanoic acid for enhanced circulation persistence in vivo

PubMed Central

Nag, Okhil K; Yadav, Vivek R; Hedrick, Andria; Awasthi, Vibhudutta

2013-01-01

We report synthesis and characterization of a novel PEG2000-conjugated hexadecylcarbamoylmethyl hexadecanoate (HDAS-PEG) as a PEG-phospholipid substitute for enhancing circulation persistence of liposomes. HDAS-PEG showed critical micelle concentration of 4.25 μM. We used post-insertion technique to introduce HDAS-PEG in outer lipid layer of the preformed liposomes. The presence of surface HDAS-PEG was confirmed by altered electrophoretic mobility, confocal microscopy and PEG estimation by ELISA. The post-inserted HDAS-PEG desorbed at approximately half the rate at which post-inserted DSPE-PEG desorbed from the liposome surface. HDAS-PEG significantly reduced liposome-induced complement activation (C4d, Bb and SC5b); HDAS-PEG was more effective than more commonly used DSPE-PEG in this capacity. For studying circulation persistence, the liposomes were labeled with 99mTc radionuclide and administered in rats. 99mTc-HDAS-PEG-liposomes showed prolonged persistence in blood as compared to that shown by 99mTc-plain liposomes. After 24 h of administration, < 1% of 99mTc-plain liposomes remained in blood, whereas approximately 28% of injected 99mTc-HDAS-PEG-liposomes were present in blood. In comparison, only 4.8% of 99mTc-DSPE-PEG-liposomes was measured in blood after 24 h. As expected, the clearance route of the liposomes was through liver and spleen. These results demonstrate the potential of a novel non-phosphoryl HDAS-PEG for surface modification of preformed liposomes with a goal of prolonging their circulation persistence and more effective inhibition of complement activation. PMID:23419666

Colonoscopy preparation: polyethylene glycol with Gatorade is as safe and efficacious as four liters of polyethylene glycol with balanced electrolytes.

PubMed

McKenna, Thomas; Macgill, Alice; Porat, Gail; Friedenberg, Frank K

2012-12-01

Four liters of polyethylene glycol 3350 (PEG) with balanced electrolytes for colonoscopy preparation has had poor acceptance. Another approach is the use of electrolyte-free PEG combined with 1.9 L of Gatorade. Despite its widespread use, there are no data on metabolic safety and minimal data on efficacy. Our aim was to assess the efficacy and electrolyte safety of these two PEG-based preparations. This was a prospective, randomized, single-blind, non-inferiority trial. Patients were randomized to 238 g PEG + 1.9 L Gatorade or 4 L of PEG-ELS containing 236 g PEG. Split dosing was not performed. On procedure day blood was drawn for basic chemistries. The primary outcome was preparation quality from procedure photos using the Boston Bowel Preparation Scale. We randomized 136 patients (66 PEG + Gatorade, 70 PEG-ELS). There were no differences in preparation scores between the two agents in the ITT analysis (7.2 ± 1.9 for PEG-ELS and 7.0 ± 2.1 for PEG + Gatorade; p = 0.45). BBPS scores were identical for those who completed the preparation and dietary instructions as directed (7.4 ± 1.7 for PEG-ELS, and 7.4 ± 1.8 for PEG + Gatorade; p = 0.98). There were no statistical differences in serum electrolytes between the two preparations. Patients who received PEG + Gatorade gave higher overall satisfaction scores for the preparation experience (p = 0.001), and had fewer adverse effects. Use of 238 g PEG + 1.9 L Gatorade appears to be safe, better tolerated, and non-inferior to 4 L PEG-ELS. This preparation may be especially useful for patients who previously tolerated PEG-ELS poorly.

Promoting Transfer in Memory Training for Older Adults

PubMed Central

Cavallini, Elena; Dunlosky, John; Bottiroli, Sara; Hertzog, Christopher; Vecchi, Tomaso

2011-01-01

Background and aims Many studies have focused on memory training in aging showing older adults can improve their performance. Unfortunately the benefits of training rarely generalize to other tasks that were not specifically trained. We investigated the benefits of instruction-based training in promoting transfer effects in older adults. Methods In Experiment 1, we evaluated transfer effects in a training group who practiced using standard mnemonics to learn paired associates and word lists, and this group was provided instructions about how the mnemonics could be used for two of the four transfer tasks (text learning, name-face learning, grocery list learning, place learning). In Experiment 2, we compared transfer effects for two different training groups: one practiced the strategies with the two trained tasks and did not receive instructions and one had the same practice but also received instructions on all the transfer tasks. Results Transfer in text learning occurred in both experiments. Such transfer is particularly interesting considering that text learning was the most dissimilar task in terms of both the nature of the materials and the underlying processes that support performance. Such transfer was reliably greater when training involved instructions about applicability than when it did not. Conclusions Instructions to use practiced strategies on new materials could be a useful technique in promoting transfer in older adults. It seems that the lack of transfer does not necessarily arise from older adults’ inabilities but instead because they do not realize that trained strategies can (or should) be applied to new materials. PMID:19966535

Promoting transfer in memory training for older adults.

PubMed

Cavallini, Elena; Dunlosky, John; Bottiroli, Sara; Hertzog, Christopher; Vecchi, Tomaso

2010-08-01

Many studies have focused on memory training in aging, showing that older adults can improve their performance. Unfortunately, the benefits of training can rarely be generalized to other tasks for which adults were not specifically trained. We investigated the benefits of instruction-based training in promoting transfer effects in older adults. In Experiment 1, we evaluated transfer effects in a training group who practiced using standard mnemonics to learn paired associates and word lists, and this group was given instructions about how the mnemonics could be used for two of the four transfer tasks (text learning, name-face learning, grocery list learning, place learning). In Experiment 2, we compared transfer effects for two different training groups: one practiced the strategies with the two trained tasks and did not receive instructions, and the other had the same practice but also received instructions on all the transfer tasks. Transfer in text learning occurred in both experiments. This transfer is particularly interesting, as text learning was the most dissimilar task in terms of both the nature of the materials and the underlying processes that support performance. The transfer was reliably greater when training involved instructions about applicability than when it did not. Instructions to use practiced strategies on new materials may be a useful technique in promoting transfer in older adults. It seems that the lack of transfer does not necessarily arise from older adults' inabilities, but because they do not realize that trained strategies can (or should) be applied to new materials.

Acquiring basic and advanced laparoscopic skills in novices using two-dimensional (2D), three-dimensional (3D) and ultra-high definition (4K) vision systems: A randomized control study.

PubMed

Abdelrahman, M; Belramman, A; Salem, R; Patel, B

2018-05-01

To compare the performance of novices in laparoscopic peg transfer and intra-corporeal suturing tasks in two-dimensional (2D), three-dimensional (3D) and ultra-high definition (4K) vision systems. Twenty-four novices were randomly assigned to 2D, 3D and 4K groups, eight in each group. All participants performed the two tasks on a box trainer until reaching proficiency. Their performance was assessed based on completion time, number of errors and number of repetitions using the validated FLS proficiency criteria. Eight candidates in each group completed the training curriculum. The mean performance time (in minutes) for the 2D group was 558.3, which was more than that of the 3D and 4K groups of 316.7 and 310.4 min respectively (P < 0.0001). The mean number of repetitions was lower for the 3D and 4K groups versus the 2D group: 125.9 and 127.4 respectively versus 152.1 (P < 0.0001). The mean number of errors was lower for the 4K group versus the 3D and 2D groups: 1.2 versus 26.1 and 50.2 respectively (P < 0.0001). The 4K vision system improved accuracy in acquiring laparoscopic skills for novices in complex tasks, which was shown in significant reduction in number of errors compared to the 3D and the 2D vision systems. The 3D and the 4K vision systems significantly improved speed and accuracy when compared to the 2D vision system based on shorter performance time, fewer errors and lesser number of repetitions. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Learning to combine high variability with high precision: lack of transfer to a different task.

PubMed

Wu, Yen-Hsun; Truglio, Thomas S; Zatsiorsky, Vladimir M; Latash, Mark L

2015-01-01

The authors studied effects of practicing a 4-finger accurate force production task on multifinger coordination quantified within the uncontrolled manifold hypothesis. During practice, task instability was modified by changing visual feedback gain based on accuracy of performance. The authors also explored the retention of these effects, and their transfer to a prehensile task. Subjects practiced the force production task for 2 days. After the practice, total force variability decreased and performance became more accurate. In contrast, variance of finger forces showed a tendency to increase during the first practice session while in the space of finger modes (hypothetical commands to fingers) the increase was under the significance level. These effects were retained for 2 weeks. No transfer of these effects to the prehensile task was seen, suggesting high specificity of coordination changes. The retention of practice effects without transfer to a different task suggests that further studies on a more practical method of improving coordination are needed.

Training self-assessment and task-selection skills to foster self-regulated learning: Do trained skills transfer across domains?

PubMed

Raaijmakers, Steven F; Baars, Martine; Paas, Fred; van Merriënboer, Jeroen J G; van Gog, Tamara

2018-01-01

Students' ability to accurately self-assess their performance and select a suitable subsequent learning task in response is imperative for effective self-regulated learning. Video modeling examples have proven effective for training self-assessment and task-selection skills, and-importantly-such training fostered self-regulated learning outcomes. It is unclear, however, whether trained skills would transfer across domains. We investigated whether skills acquired from training with either a specific, algorithmic task-selection rule or a more general heuristic task-selection rule in biology would transfer to self-regulated learning in math. A manipulation check performed after the training confirmed that both algorithmic and heuristic training improved task-selection skills on the biology problems compared with the control condition. However, we found no evidence that students subsequently applied the acquired skills during self-regulated learning in math. Future research should investigate how to support transfer of task-selection skills across domains.

Quantitative analysis of PEG-functionalized colloidal gold nanoparticles using charged aerosol detection.

PubMed

Smith, Mackensie C; Crist, Rachael M; Clogston, Jeffrey D; McNeil, Scott E

2015-05-01

Surface characteristics of a nanoparticle, such as functionalization with polyethylene glycol (PEG), are critical to understand and achieve optimal biocompatibility. Routine physicochemical characterization such as UV-vis spectroscopy (for gold nanoparticles), dynamic light scattering, and zeta potential are commonly used to assess the presence of PEG. However, these techniques are merely qualitative and are not sensitive enough to distinguish differences in PEG quantity, density, or presentation. As an alternative, two methods are described here which allow for quantitative measurement of PEG on PEGylated gold nanoparticles. The first, a displacement method, utilizes dithiothreitol to displace PEG from the gold surface. The dithiothreitol-coated gold nanoparticles are separated from the mixture via centrifugation, and the excess dithiothreitol and dissociated PEG are separated through reversed-phase high-performance liquid chromatography (RP-HPLC). The second, a dissolution method, utilizes potassium cyanide to dissolve the gold nanoparticles and liberate PEG. Excess CN(-), Au(CN)2 (-), and free PEG are separated using RP-HPLC. In both techniques, the free PEG can be quantified against a standard curve using charged aerosol detection. The displacement and dissolution methods are validated here using 2-, 5-, 10-, and 20-kDa PEGylated 30-nm colloidal gold nanoparticles. Further value in these techniques is demonstrated not only by quantitating the total PEG fraction but also by being able to be adapted to quantitate the free unbound PEG and the bound PEG fractions. This is an important distinction, as differences in the bound and unbound PEG fractions can affect biocompatibility, which would not be detected in techniques that only quantitate the total PEG fraction.

Temperature-Dependent Implicit-Solvent Model of Polyethylene Glycol in Aqueous Solution.

PubMed

Chudoba, Richard; Heyda, Jan; Dzubiella, Joachim

2017-12-12

A temperature (T)-dependent coarse-grained (CG) Hamiltonian of polyethylene glycol/oxide (PEG/PEO) in aqueous solution is reported to be used in implicit-solvent material models in a wide temperature (i.e., solvent quality) range. The T-dependent nonbonded CG interactions are derived from a combined "bottom-up" and "top-down" approach. The pair potentials calculated from atomistic replica-exchange molecular dynamics simulations in combination with the iterative Boltzmann inversion are postrefined by benchmarking to experimental data of the radius of gyration. For better handling and a fully continuous transferability in T-space, the pair potentials are conveniently truncated and mapped to an analytic formula with three structural parameters expressed as explicit continuous functions of T. It is then demonstrated that this model without further adjustments successfully reproduces other experimentally known key thermodynamic properties of semidilute PEG solutions such as the full equation of state (i.e., T-dependent osmotic pressure) for various chain lengths as well as their cloud point (or collapse) temperature.

Training of resistance to proactive interference and working memory in older adults: a randomized double-blind study.

PubMed

Loosli, Sandra V; Falquez, Rosalux; Unterrainer, Josef M; Weiller, Cornelius; Rahm, Benjamin; Kaller, Christoph P

2016-03-01

Working memory (WM) performance is often decreased in older adults. Despite the growing popularity of WM trainings, underlying mechanisms are still poorly understood. Resistance to proactive interference (PI) constitutes a candidate process that contributes to WM performance and might influence training or transfer effects. Here, we investigated whether PI resistance can be enhanced in older adults using a WM training with specifically increased PI-demands. Further, we investigated whether potential effects of such a training were stable and entailed any transfer on non-trained tasks. Healthy old adults (N = 25, 68.8 ± 5.5 years) trained with a recent-probes and an n-back task daily for two weeks. Two different training regimens (high vs. low PI-amount in the tasks) were applied as between-participants manipulation, to which participants were randomly assigned. Near transfer tasks included interference tasks; far transfer tasks assessed fluid intelligence (gF) or speed. Immediate transfer was assessed directly after training; a follow-up measurement was conducted after two months. Both groups similarly improved in PI resistance in both training tasks. Thus, PI susceptibility was generally reduced in the two training groups and there was no difference between WM training with high versus low PI demands. Further, there was no differential near or far transfer on non-trained tasks, neither immediately after the training nor in the follow-up. PI-demands in WM training tasks do not seem critical for enhancing WM performance or PI resistance in older adults. Instead, improved resistance to PI appears to be an unspecific side-effect of a WM training.

Influence of different peg length in glenoid bone loss: A biomechanical analysis regarding primary stability of the glenoid baseplate in reverse shoulder arthroplasty.

PubMed

Königshausen, M; Jettkant, B; Sverdlova, N; Ehlert, C; Gessmann, J; Schildhauer, T A; Seybold, D

2015-01-01

There is no biomechanical basis to determine the influence of different length of the central peg of the baseplate anchored within the native scapula in glenoid defect reconstruction in cases of degenerative or posttraumatic glenoid bone loss in reversed shoulder arthroplasty. The purpose of this study was to analyse the stability of different peg lengths used in glenoid bone loss in reversed shoulder arthroplasty. Different lengths of metaglene pegs with different depths of peg anchorage performed with or without metaglene screws in sawbone foam blocks were loaded in vertical and horizontal directions for differentiating load capacities. Simulated physiological loadings were then applied to the peg implants to determine the limits of loading in each depth of anchorage. The loading capacity of the implant was reduced as less of the peg was anchored. The vertically loaded implants showed a significantly higher stability, in contrast to those loaded horizontally at a corresponding peg length and depth of anchorage (p < 0.05). The tests revealed that the metaglene screws are more essential for primary stability than is the peg particularly in the vertically directed loadings (2/3 anchored: peg contributed to 28% of the stability, 1/3 anchorage: peg contributed to 12%). Under the second test conditions, the lowest depth of peg anchorage (1/3) resulted in 322 Newtons [N] in the long peg with a vertical loading direction, and in 130 N in the long peg with a horizontal loading direction (p < 0.05). The pegs should be anchored as deeply as possible into the native scapula bone stock. The metaglene screws play a major role in the initial stability, in contrast to the peg, and they become more important when the depth of the peg anchorage is reduced. If possible, four metaglene screws should be used in cases of uncontained bone loss to guarantee the highest stability.

Investigation of PEG crystallization in frozen and freeze-dried PEGylated recombinant human growth hormone-sucrose systems: implications on storage stability.

PubMed

Bhatnagar, Bakul S; Martin, Susan W H; Hodge, Tamara S; Das, Tapan K; Joseph, Liji; Teagarden, Dirk L; Shalaev, Evgenyi Y; Suryanarayanan, Raj

2011-08-01

The objectives of the current study were to investigate (i) the phase behavior of a PEGylated recombinant human growth hormone (PEG-rhGH, ∼60 kDa) during freeze-drying and (ii) its storage stability. The phase transitions during freeze-thawing of an aqueous solution containing PEG-rhGH and sucrose were characterized by differential scanning calorimetry. Finally, PEG-rhGH and sucrose formulations containing low, medium, and high polyethylene glycol (PEG) to sucrose ratios were freeze-dried in dual-chamber syringes and stored at 4°C and 25°C. Chemical decomposition (methionine oxidation and deamidation) and irreversible aggregation were characterized by size-exclusion and ion-exchange chromatography, and tryptic mapping. PEG crystallization was facilitated when it was covalently linked with rhGH. When the solutions were frozen, phase separation into PEG-rich and sucrose-rich phases facilitated PEG crystallization and the freeze-dried cake contained crystalline PEG. Annealing caused PEG crystallization and when coupled with higher drying temperatures, the primary drying time decreased by up to 51%. When the freeze-dried cakes were stored at 4°C, while there was no change in the purity of the PEG-rhGH monomer, deamidation was highest in the formulations with the lowest PEG to sucrose ratio. When stored at 25°C, this composition also showed the most pronounced decrease in monomer purity, the highest level of aggregation, and deamidation. Furthermore, an increase in PEG crystallinity during storage was accompanied by a decrease in PEG-rhGH stability. Interestingly, during storage, there was no change in PEG crystallinity in formulations with medium and high PEG to sucrose ratios. Although PEG crystallization during freeze-drying did not cause protein degradation, crystallization during storage might have influenced protein stability. Copyright © 2011 Wiley-Liss, Inc.

Artesunate-modified nano-graphene oxide for chemo-photothermal cancer therapy

PubMed Central

Pang, Yilin; Mai, Zihao; Wang, Bin; Wang, Lu; Wu, Liping; Wang, Xiaoping; Chen, Tongsheng

2017-01-01

Poor water-solubility of artesunate (ARS) hampers its clinical application. We here covalently linked ARS to PEGylated nanographene oxide (nGO-PEG) to obtain ARS-modified nGO-PEG (nGO-PEG-ARS) with excellent photothermal effect and dispersibility in physiological environment. nGO-PEG-ARS induced reactive oxygen species (ROS) and peroxynitrite (ONOO─) generations. Although nGO-PEG with near-infrared (NIR) irradiation did not induce cytotoxicity, the photothermal effect of nGO-PEG under NIR irradiation enhanced not only cell uptake but also ONOO─ generation of nGO-PEG-ARS, resulting in the synergistic chemo-photothermal effect of nGO-PEG-ARS in killing HepG2 cells. Pretreatment with Fe(III) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato chloride (FeTTPS, a ONOO─ scavenger) instead of antioxidant N-Acetyle-Cysteine (NAC, an ROS scavenger) significantly blocked the cytotoxicity of nGO-PEG-ARS with or without NIR irradiation, demonstrating that ONOO─ instead of ROS dominated the synergistic chemo-photothermal anti-cancer action of nGO-PEG-ARS. nGO-PEG-ARS with NIR irradiation resulted in a complete tumor cure within 15 days earlier than other treatment groups, and did not induce apparent histological lesion for the mice treated with nGO-PEG-ARS with or without NIR irradiation for 30 days, further proving the synergistic chemo-photothermal anti-cancer effect of nGO-PEG-ARS. Collectively, nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer therapy. PMID:29212190

Hyaluronic Acid Hydrogel Functionalized with Self-Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis.

PubMed

Kang, Mi-Lan; Jeong, Se-Young; Im, Gun-Il

2017-07-01

Synthetic hyaluronic acid (HA) containing a covalently integrated drug is capable of releasing therapeutic molecules and is an attractive candidate for the intra-articular treatment of osteoarthritis (OA). Herein, self-assembled PEGylated kartogenin (PEG/KGN) micelles consisting of hydrophilic polyethylene glycol (PEG) and hydrophobic KGN, which has been shown to induce chondrogenesis in human mesenchymal stem cells, were prepared by covalent crosslinking. HA hydrogels containing PEG/KGN micelles (HA/PEG/KGN) were prepared by covalently bonding PEG chains to HA. The physicochemical properties of the HA/PEG/KGN conjugate gels were investigated using Fourier transform infrared spectroscopy, 1 H NMR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). HA/PEG/KGN gels exhibited larger micelles in aqueous solution than PEG/KGN. SEM images of PEG/KGN micelles showed a dark core and a bright shell, whereas PEG/KGN micelles covalently integrated into HA had an irregular oval shape. Covalent integration of PEG/KGN micelles in HA hydrogels significantly reduced drug release rates and provided sustained release over a prolonged period of time. HA/PEG/KGN hydrogels were degradable enzymatically by collagenase and hyaluronidase in vitro. Injection of HA/PEG/KGN hydrogels into articular cartilage significantly suppressed the progression of OA in rats compared with free-HA hydrogel injection. These results suggest that the HA/PEG/KGN hydrogels have greater potency than free-HA hydrogels against OA as biodegradable synthetic therapeutics.

Ferris Wheels and Filling Bottles: A Case of a Student's Transfer of Covariational Reasoning across Tasks with Different Backgrounds and Features

ERIC Educational Resources Information Center

Johnson, Heather Lynn; McClintock, Evan; Hornbein, Peter

2017-01-01

Using an actor-oriented perspective on transfer, we report a case of a student's transfer of covariational reasoning across tasks involving different backgrounds and features. In this study, we investigated the research question: How might a student's covariational reasoning on Ferris wheel tasks, involving attributes of distance, width, and…

Application of a Curriculum Hierarchy Evaluation (CHE) Model to Sequentially Arranged Tasks.

ERIC Educational Resources Information Center

O'Malley, J. Michael

A curriculum hierarchy evaluation (CHE) model was developed by combining a transfer paradigm with an aptitude-treatment-task interaction (ATTI) paradigm. Positive transfer was predicted between sequentially arranged tasks, and a programed or nonprogramed treatment was predicted to interact with aptitude and with tasks. Eighteen four and five…

Task specificity of attention training: the case of probability cuing

PubMed Central

Jiang, Yuhong V.; Swallow, Khena M.; Won, Bo-Yeong; Cistera, Julia D.; Rosenbaum, Gail M.

2014-01-01

Statistical regularities in our environment enhance perception and modulate the allocation of spatial attention. Surprisingly little is known about how learning-induced changes in spatial attention transfer across tasks. In this study, we investigated whether a spatial attentional bias learned in one task transfers to another. Most of the experiments began with a training phase in which a search target was more likely to be located in one quadrant of the screen than in the other quadrants. An attentional bias toward the high-probability quadrant developed during training (probability cuing). In a subsequent, testing phase, the target's location distribution became random. In addition, the training and testing phases were based on different tasks. Probability cuing did not transfer between visual search and a foraging-like task. However, it did transfer between various types of visual search tasks that differed in stimuli and difficulty. These data suggest that different visual search tasks share a common and transferrable learned attentional bias. However, this bias is not shared by high-level, decision-making tasks such as foraging. PMID:25113853

Robust and specific ratiometric biosensing using a copper-free clicked quantum dot-DNA aptamer sensor

NASA Astrophysics Data System (ADS)

Zhang, Haiyan; Feng, Guoqiang; Guo, Yuan; Zhou, Dejian

2013-10-01

We report herein the successful preparation of a compact and functional CdSe-ZnS core-shell quantum dot (QD)-DNA conjugate via highly efficient copper-free ``click chemistry'' (CFCC) between a dihydro-lipoic acid-polyethylene glycol-azide (DHLA-PEG-N3) capped QD and a cyclooctyne modified DNA. This represents an excellent balance between the requirements of high sensitivity, robustness and specificity for the QD-FRET (Förster resonance energy transfer) based sensor as confirmed by a detailed FRET analysis on the QD-DNA conjugate, yielding a relatively short donor-acceptor distance of ~5.8 nm. We show that this CFCC clicked QD-DNA conjugate is not only able to retain the native fluorescence quantum yield (QY) of the parent DHLA-PEG-N3 capped QD, but also well-suited for robust and specific biosensing; it can directly quantitate, at the pM level, both labelled and unlabelled complementary DNA probes with a good SNP (single-nucleotide polymorphism) discrimination ability in complex media, e.g. 10% human serum via target-binding induced FRET changes between the QD donor and the dye acceptor. Furthermore, this sensor has also been successfully exploited for the detection, at the pM level, of a specific protein target (thrombin) via the encoded anti-thrombin aptamer sequence in the QD-DNA conjugate.We report herein the successful preparation of a compact and functional CdSe-ZnS core-shell quantum dot (QD)-DNA conjugate via highly efficient copper-free ``click chemistry'' (CFCC) between a dihydro-lipoic acid-polyethylene glycol-azide (DHLA-PEG-N3) capped QD and a cyclooctyne modified DNA. This represents an excellent balance between the requirements of high sensitivity, robustness and specificity for the QD-FRET (Förster resonance energy transfer) based sensor as confirmed by a detailed FRET analysis on the QD-DNA conjugate, yielding a relatively short donor-acceptor distance of ~5.8 nm. We show that this CFCC clicked QD-DNA conjugate is not only able to retain the native fluorescence quantum yield (QY) of the parent DHLA-PEG-N3 capped QD, but also well-suited for robust and specific biosensing; it can directly quantitate, at the pM level, both labelled and unlabelled complementary DNA probes with a good SNP (single-nucleotide polymorphism) discrimination ability in complex media, e.g. 10% human serum via target-binding induced FRET changes between the QD donor and the dye acceptor. Furthermore, this sensor has also been successfully exploited for the detection, at the pM level, of a specific protein target (thrombin) via the encoded anti-thrombin aptamer sequence in the QD-DNA conjugate. Electronic supplementary information (ESI) available: Details on the synthesis, purification and characterisation of the DHLA-PEG600-N3, cyclooctyne-DNA, and QD-TBA20 conjugates as well as all supporting figures and tables. See DOI: 10.1039/c3nr02897f

Strengthened effective connectivity underlies transfer of working memory training to tests of short-term memory and attention.

PubMed

Kundu, Bornali; Sutterer, David W; Emrich, Stephen M; Postle, Bradley R

2013-05-15

Although long considered a natively endowed and fixed trait, working memory (WM) ability has recently been shown to improve with intensive training. What remains controversial and poorly understood, however, are the neural bases of these training effects and the extent to which WM training gains transfer to other cognitive tasks. Here we present evidence from human electrophysiology (EEG) and simultaneous transcranial magnetic stimulation and EEG that the transfer of WM training to other cognitive tasks is supported by changes in task-related effective connectivity in frontoparietal and parieto-occipital networks that are engaged by both the trained and transfer tasks. One consequence of this effect is greater efficiency of stimulus processing, as evidenced by changes in EEG indices of individual differences in short-term memory capacity and in visual search performance. Transfer to search-related activity provides evidence that something more fundamental than task-specific strategy or stimulus-specific representations has been learned. Furthermore, these patterns of training and transfer highlight the role of common neural systems in determining individual differences in aspects of visuospatial cognition.

Strengthened effective connectivity underlies transfer of working memory training to tests of short-term memory and attention

PubMed Central

Kundu, Bornali; Sutterer, David W.; Emrich, Stephen M.; Postle, Bradley R.

2013-01-01

Although long considered a natively endowed and fixed trait, working memory (WM) ability has recently been shown to improve with intensive training. What remains controversial and poorly understood, however, are the neural bases of these training effects, and the extent to which WM training gains transfer to other cognitive tasks. Here we present evidence from human electrophysiology (EEG) and simultaneous transcranial magnetic stimulation (TMS) and EEG that the transfer of WM training to other cognitive tasks is supported by changes in task-related effective connectivity in frontoparietal and parietooccipital networks that are engaged by both the trained and transfer tasks. One consequence of this effect is greater efficiency of stimulus processing, as evidenced by changes in EEG indices of individual differences in short-term memory capacity and in visual search performance. Transfer to search-related activity provides evidence that something more fundamental than task-specific strategy or stimulus-specific representations have been learned. Furthermore, these patterns of training and transfer highlight the role of common neural systems in determining individual differences in aspects of visuospatial cognition. PMID:23678114

Final report on the safety assessment of Triethylene Glycol and PEG-4.

PubMed

2006-01-01

Triethylene Glycol and PEG-4 (polyethylene glycol) are polymers of ethylene oxide alcohol. Triethylene Glycol is a specific three-unit chain, whereas PEG-4 is a polymer with an average of four units, but may contain polymers ranging from two to eight ethylene oxide units. In the same manner, other PEG compounds, e.g., PEG-6, are mixtures and likely contain some Triethylene Glycol and PEG-4. Triethylene Glycol is a fragrance ingredient and viscosity decreasing agent in cosmetic formulations, with a maximum concentration of use of 0.08% in skin-cleansing products. Following oral doses, Triethylene Glycol and its metabolites are excreted primarily in urine, with small amounts released in feces and expired air. With oral LD50 values in rodents from 15 to 22 g/kg, this compound has little acute toxicity. Rats given short term oral doses of 3% in water showed no signs of toxicity, whereas all rats given 10% died by the 12th day of exposure. At levels up to 1 g/m3, rats exposed to aerosolized Triethylene Glycol for 6 h per day for 9 days showed no signs of toxicity. Rats fed a diet containing 4% Triethylene Glycol for 2 years showed no signs of toxicity. There were no treatment-related effects on rats exposed to supersaturated Triethylene Glycol vapor for 13 months nor in rats that consumed 0.533 cc Triethylene Glycol per day in drinking water for 13 months. Triethylene Glycol was not irritating to the skin of rabbits and produced only minimal injury to the eye. In reproductive and developmental toxicity studies in rats and mice, Triethylene Glycol did not produce biologically significant embryotoxicity or teratogenicity. However, some maternal toxicity was seen in dams given 10 ml/kg/day during gestation. Triethylene Glycol was not mutagenic or genotoxic in Ames-type assays, the Chinese hamster ovary mutation assay, and the sister chromatid exchange assays. PEG-4 is a humectant and solvent in cosmetic products, with a maximum concentration of use of 20% in the "other manicuring preparations" product category. This ingredient, with an oral LD50 in rats of 32.77 g/kg, has low acute toxicity. Rats given up to 50,000 ppm PEG-4 in drinking water for 5 days showed no permanent signs of toxicity. Rats given daily oral doses up to 2 g/kg/day of PEG-4 for 33 days showed no signs of toxicity. Undiluted PEG-4 produced only minimal injury to the rabbit eye. PEG-4 was not mutagenic in Ames-type assays, did not induce chromosome aberration in an in vivo bone marrow assay, and was negative for genotoxicity in a dominant lethal assay using rats. Other PEG compounds, which have previously been reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, e.g., PEG-6, are mixtures that likely include Triethylene Glycol and PEG-4, so these data were also considered. PEG-6 and PEG-8 were not dermal irritants in several rabbit studies. PEG-2 Stearate had a potential for slight irritation in rabbits but was not a sensitizer in guinea pigs. PEG-2 Cocamine was a moderate irritant in rabbits, producing severe erythema. In one dermal study, PEG-2 Cocamine was determined to be corrosive to rabbit skin, causing eschar and necrosis. PEG-6 and PEG-8 caused little to no ocular irritation. PEG-8 was not mutagenic or genotoxic in a Chinese hamster ovary assay, a sister-chromatid exchange assay, and in an unscheduled DNA synthesis assay. In clinical studies on normal skin, PEG-6 and PEG-8 caused mild cases of immediate hypersensitivity; PEG-8 was not a sensitizer; PEG-2 Stearate was not an irritant, a sensitizer, or a photosensitizer; and PEG-6 Stearate was not an irritant or sensitizer. In damaged skin, cases of systemic toxicity and contact dermatitis in burn patients were attributed to a PEG-based topical ointment. The CIR Expert Panel acknowledged the lack of dermal sensitization data for Triethylene Glycol and dermal irritation and sensitization data for PEG-4. That PEG-6, PEG-8, and PEG-2 Stearate were not irritants or sensitizers suggested that Triethylene Glycol and PEG-4 also would not be irritants or sensitizers, and the absence of any reported reactions in the case literature and the professional experience of the Expert Panel further supported the absence of any significant sensitization potential. The need for additional data to demonstrate the safety of PEGs Cocamine was related to the Cocamine moiety and is not relevant here. The Panel reminded formulators of cosmetic products that, as with other PEG compounds, Triethylene Glycol and PEG-4 should not be used on damaged skin because of cases of systemic toxicity and contact dermatitis in burn patients have been attributed to a PEG-based topical ointment. Based on its consideration of the available information, the CIR Expert Panel concluded that Triethylene Glycol and PEG-4 are safe as cosmetic ingredients in the present practices and concentrations of use as described in this safety assessment.

Improved Micellar Formulation for Enhanced Delivery for Paclitaxel.

PubMed

Xu, Jieni; Zhang, Xiaolan; Chen, Yichao; Huang, Yixian; Wang, Pengcheng; Wei, Yuan; Ma, Xiaochao; Li, Song

2017-01-03

We have previously improved the bioactivity of PEG 5k -FTS 2 system by incorporating disulfide bond (PEG 5k -S-S-FTS 2 ) to facilitate the release of farnesyl thiosalicylic acid (FTS).1 Later, fluorenylmethyloxycarbonyl (Fmoc) moiety has been introduced to PEG 5k -FTS 2 system (PEG 5k -Fmoc-FTS 2 ) in order to enhance drug loading capacity (DLC) and formulation stability.2 In this study, we have brought in both disulfide linkage and Fmoc group to PEG 5k -FTS 2 to form a simple PEG 5k -Fmoc-S-S-FTS 2 micellar system. PEG 5k -Fmoc-S-S-FTS 2 conjugate formed filamentous micelles with a ∼10-fold decrease in critical micellar concentration (CMC). Compared with PEG 5k -Fmoc-FTS 2 , our novel system exhibited further strengthened DLC and colloidal stability. More FTS was freed from PEG 5k -Fmoc-S-S-FTS 2 in treated tumor cells compared to PEG 5k -Fmoc-FTS 2 , which was correlated to an increased cytotoxicity of our new carrier in these cancer cells. After loading Paclitaxel (PTX) into PEG 5k -Fmoc-S-S-FTS 2 micelles, it showed more potent efficiency in inhibition of tumor cell proliferation than Taxol and PTX-loaded PEG 5k -Fmoc-FTS 2 . PTX release kinetics of PTX/PEG 5k -Fmoc-S-S-FTS 2 was much slower than that of Taxol and PTX/PEG 5k -Fmoc-FTS 2 in normal release medium. In contrast, in glutathione (GSH)-containing medium, PTX in PEG 5k -Fmoc-S-S-FTS 2 micelles revealed faster and more complete release. Pharmacokinetics and tissue distribution study showed that our PEG 5k -Fmoc-S-S-FTS 2 system maintained PTX in circulation for a longer time and delivered more PTX to tumor sites with less accumulation in major organs. Finally, PTX-loaded PEG 5k -Fmoc-S-S-FTS 2 micelles resulted in a superior therapeutic effect in vivo compared to Taxol and PTX formulated in PEG 5k -Fmoc-FTS 2 micelles.

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy

PubMed Central

Valiante, Flavio; Bellumat, Angelo; De Bona, Manuela; De Boni, Michele

2013-01-01

AIM: To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. METHODS: This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. Interventions: BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. RESULTS: Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). CONCLUSION: BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy. PMID:24023492

Randomised clinical trial: low-volume bowel preparation for colonoscopy - a comparison between two different PEG-based formulations.

PubMed

Repici, A; Cestari, R; Annese, V; Biscaglia, G; Vitetta, E; Minelli, L; Trallori, G; Orselli, S; Andriulli, A; Hassan, C

2012-10-01

Low-volume bowel preparations with polyethylene glycol (PEG) have been shown to provide an equivalent cleansing with improved tolerability as compared with standard PEG bowel preparation for colonoscopy. A new iso-osmotic sulphate-free formulation of PEG-Citrate-Simethicone (PEG-CS) in combination with bisacodyl has been recently developed. To compare the quality of bowel cleansing with PEG-CS with bisacodyl vs. PEG-Ascorbate (PEG-ASC) in adult out-patients undergoing colonoscopy. Randomised, observer-blind, parallel group study in adult out-patients undergoing colonoscopy in five Italian centres. Both preparations were taken the evening before the procedure. Subjects were instructed to take 2-4 tablets of 5 mg bisacodyl at 16:00 hours and 2 L of PEG-CS at 20:00 hours or 2 L of PEG-ASC plus 1 L of additional water the day before colonoscopy. Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale (≥6 scores were considered as 'clinical success'), and mucosal visibility according to a 3-point scale. Tolerability, acceptability and compliance were also evaluated. Four hundred and eight patients were randomly allocated to PEG-CS and bisacodyl (n = 204, male patient 48%, mean age 59.1 years) or PEG-ASC (n = 204, male patient 51%, age 59.4 years). In the planned per-protocol analysis, the rate of successful preparation was 79.1% following PEG-CS with bisacodyl, and 70% following PEG-ASC (P < 0.05). Mucosal visibility was evaluated as optimal in 56.1% in the PEG-CS and bisacodyl and 46.3% in the PEG-ASC group (P < 0.05). There were no serious adverse events (AE) in each of the two experimental groups. Two subjects in the PEG-ASC group discontinued the study because of AE. Polyethylene glycol-Citrate-Simethicone in combination with bisacodyl was more effective for bowel cleansing than PEG-ASC for out-patient colonoscopy. Tolerability, safety, acceptability and compliance of the two low-volume bowel preparations were similar. © 2012 Blackwell Publishing Ltd.

The Institutional Organisation of Knowledge Transfer and Its Implications

ERIC Educational Resources Information Center

van der Heide, Sjors; van der Sijde, Peter C.; Terlouw, Cees

2008-01-01

How do European universities organise the knowledge transfer (KT) task? We consider the institutional organisation of knowledge transfer as encompassing 1) the knowledge transfer office structure, i.e. the way universities have embedded and organise their KT activities, 2) the focus towards the KT task, linked to the KT strategy, and 3) the KT…

Assessing the California Transfer Function: The Transfer Rate and Its Measurement. Conclusions of the Data Needs Task Force.

ERIC Educational Resources Information Center

Intersegmental Coordinating Council, Sacramento, CA.

In the fall of 1989, the Intersegmental Coordinating Council organized the Data Needs Task Force (DNTF) to determine the feasibility of establishing a transfer rate definition. Specifically, the DNTF was charged with defining the information needed to strengthen intersegmental transfer programs, establishing common definitions (including…

Unexpected electronic perturbation effects of simple PEG environments on the optical properties of small cadmium chalcogenide clusters

NASA Astrophysics Data System (ADS)

Fukunaga, Naoto; Konishi, Katsuaki

2015-12-01

Poly(ethylene glycol) (PEG) has been widely used for the surface protection of inorganic nanoobjects because of its virtually `inert' nature, but little attention has been paid to its inherent electronic impacts on inorganic cores. Herein, we definitively show, through studies on optical properties of a series of PEG-modified Cd10Se4(SR)10 clusters, that the surrounding PEG environments can electronically affect the properties of the inorganic core. For the clusters with PEG units directly attached to an inorganic core (R = (CH2CH2O)nOCH3, 1-PEGn, n = 3, ~7, ~17, ~46), the absorption bands, associated with the low-energy transitions, continuously blue-shifted with the increasing PEG chain length. The chain length dependencies were also observed in the photoluminescence properties, particularly in the excitation spectral profiles. By combining the spectral features of several PEG17-modified clusters (2-Cm-PEG17 and 3) whose PEG and core units are separated by various alkyl chain-based spacers, it was demonstrated that sufficiently long PEG units, including PEG17 and PEG46, cause electronic perturbations in the cluster properties when they are arranged near the inorganic core. These unique effects of the long-PEG environments could be correlated with their large dipole moments, suggesting that the polarity of the proximal chemical environment is critical when affecting the electronic properties of the inorganic cluster core.Poly(ethylene glycol) (PEG) has been widely used for the surface protection of inorganic nanoobjects because of its virtually `inert' nature, but little attention has been paid to its inherent electronic impacts on inorganic cores. Herein, we definitively show, through studies on optical properties of a series of PEG-modified Cd10Se4(SR)10 clusters, that the surrounding PEG environments can electronically affect the properties of the inorganic core. For the clusters with PEG units directly attached to an inorganic core (R = (CH2CH2O)nOCH3, 1-PEGn, n = 3, ~7, ~17, ~46), the absorption bands, associated with the low-energy transitions, continuously blue-shifted with the increasing PEG chain length. The chain length dependencies were also observed in the photoluminescence properties, particularly in the excitation spectral profiles. By combining the spectral features of several PEG17-modified clusters (2-Cm-PEG17 and 3) whose PEG and core units are separated by various alkyl chain-based spacers, it was demonstrated that sufficiently long PEG units, including PEG17 and PEG46, cause electronic perturbations in the cluster properties when they are arranged near the inorganic core. These unique effects of the long-PEG environments could be correlated with their large dipole moments, suggesting that the polarity of the proximal chemical environment is critical when affecting the electronic properties of the inorganic cluster core. Electronic supplementary information (ESI) available: Details of synthetic procedures and characterisation data of the PEGylated thiols and clusters and additional absorption, photoluminescence emission and excitation spectral data. See DOI: 10.1039/c5nr06307h

Sensitive and rapid detection of anti-PEG in blood using surface plasmon resonance sensor (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, Fang; Jiang, Shaoyi; Yu, Qiuming

2016-03-01

Polyethylene glycol (PEG) is widely used to modify many therapeutic proteins and nanoparticles to reduce their immunogenicity and to improve their pharmacokinetic and therapeutic properties. It is generally accepted that PEG is non-immunogenic and non-antigenic. However, an emerging of literature and studies shows that the immune system can generate specific antibodies binding PEG. These anti-PEG antibodies not only correlate with adverse reactions appeared after patient infusions, but are also found to be the reason for therapeutic efficacy loss during chronical administrations. In addition, because of constant exposure to PEG in daily consumer products including detergents, processed food and cosmetics, a substantial proportion of the population has likely developed anti-PEG immunity. Thus a method to quickly and accurately measure the anti-PEG antibody level is desired. Nevertheless, the gold standard to detect anti-PEG antibodies is ELISA, which is costly and time-consuming especially for quantification. Herein, we demonstrated the anti-PEG measurement in blood serum using surface plasmon resonance (SPR) sensor. Several PEG-based surface functionalization on SPR sensor chip were studied in terms of protein resistance and the limit of detection (LOD) of anti-PEG. The quantitative detection can be achieved in less than 30 min with LOD comparable to ELISA. Furthermore, the IgG and IgM of anti-PEG can be differentiated by following the secondary antibody.

Synthesis, characterization, and biocompatibility of alternating block polyurethanes based on PLA and PEG.

PubMed

Mei, Tingzhen; Zhu, Yonghe; Ma, Tongcui; He, Tao; Li, Linjing; Wei, Chiju; Xu, Kaitian

2014-09-01

A series of alternating block polyurethanes (abbreviated as PULA-alt-PEG) and random block polyurethanes (abbreviated as PULA-ran-PEG) based on poly(L-lactic acid) (PLA) and poly(ethylene glycol) (PEG) were synthesized. The differences of PULA-alt/ran-PEG chemical structure, molecular weight, distribution, thermal properties, mechanical properties and static contact angle were systematically investigated. The PULA-alt/ran-PEG polyurethanes exhibited low T(g) (-47.3 ∼ -34.4°C), wide mechanical properties (stress σ(t): 4.6-32.6 MPa, modulus E: 11.4-323.9 MPa and strain ε: 468-1530%) and low water contact angle (35.4-51.4°). Scanning electron microscope (SEM) observation showed that PULA-alt-PEG film displays rougher and more patterned surface morphology than PULA-ran-PEG does, due to more regular structures of PULA-alt-PEG. Hydrolytic degradation shows that degradation rate of random block polyurethane series PULA-ran-PEG is higher than the alternating counterpart PULA-alt-PEG. PLA segment degradation is faster than urethane linkage and PEG segment almost does not degrade in the buffer solution. Platelet adhesion study showed that all the polyurethanes possess excellent hemocompatibility. The cell culture assay revealed that PULA-alt/ran-PEG polyurethanes were cell inert and unfavorable for the attachment of rat glial cell due to the hydrophilic characters of the materials. © 2013 Wiley Periodicals, Inc.

The effect of polyoxyethylene polymers on the transport of ranitidine in Caco-2 cell monolayers.

PubMed

Ashiru-Oredope, Diane A I; Patel, Nilesh; Forbes, Ben; Patel, Rajesh; Basit, Abdul W

2011-05-16

Previous in vivo studies using PEG 400 showed an enhancement in the bioavailability of ranitidine. This study investigated the effect of PEG 200, 300 and 400 on ranitidine transport across Caco-2 cells. The effect of PEG polymers (20%, v/v) on the bi-directional flux of (3)H-ranitidine across Caco-2 cell monolayers was measured. The concentration dependence of PEG 400 effects on ranitidine transport was also studied. A specific screen for P-glycoprotein (P-gp) activity was used to test for an interaction between PEG and P-gp. In the absence of PEG, ranitidine transport showed over 5-fold greater flux across Caco-2 monolayers in the secretory than the absorptive direction; efflux ratio 5.38. PEG 300 and 400 significantly reduced this efflux ratio (p<0.05), whereas PEG 200 had no effect (p>0.05). In concordance, PEG 300 and 400 showed an interaction with the P-gp transporter, whereas PEG 200 did not. Interestingly, with PEG 400 a non-linear concentration dependence was seen for the inhibition of the efflux ratio of ranitidine, with a maxima at 1%, v/v (p<0.05). The inhibition of ranitidine efflux by PEG 300 and 400 which interact with P-gp provides a mechanism that may account for the observations of ranitidine absorption enhancement by PEG 400 in vivo. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhanced circulation half-life of site-specific PEGylated rhG-CSF: optimization of PEG molecular weight.

PubMed

Zhai, Yanqin; Zhao, Yongjiang; Lei, Jiandu; Su, Zhiguo; Ma, Guanghui

2009-07-15

Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, the high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxy-poly(ethylene glycol)-propionaldehyde (mPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity, separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and mono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF. Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy.

Differences in taste between two polyethylene glycol preparations.

PubMed

Szojda, Maria M; Mulder, Chris J J; Felt-Bersma, Richelle J F

2007-12-01

Polyethylene glycol preparations (PEG) are increasingly used for chronic constipation in both adults and children. There are some suggestions that PEG 4000 with orange flavour (Forlax) tastes better than PEG 3350 which contains salt (Movicolon). Poor taste is an important factor for non-compliance and is one of the leading causes of therapy failure. The aim of the study was to compare the taste of two commonly used PEG preparations, PEG 4000 and PEG 3350. A double-blind, cross over randomised trial. A hundred people were recruited by advertisement. All tasted both preparations without swallowing and after tasting each of the preparations, they rinsed their mouths. Then a score, on a 5-point scale, was given for both preparations. 100 volunteers were included (27 males and 73 females, mean age 36). The taste score for PEG 4000 (mean 3.9, SD 0.7) was significantly better than for PEG 3350 (mean 2.7, SD 0.7) (p<0.0001, Wilcoxon matched pairs test). No difference in gender or age was observed. The volunteers which tasted PEG 3350 liked it more, when they tasted it first rather than when they tasted it after PEG 4000 (p<0.0001). The order in which volunteers tested PEG 4000 had no influence on the taste results. PEG 4000 tastes better than PEG 3350. This may have implications for patient compliance and effectiveness of treatment in patients with chronic constipation.

Predictive Factors for Prophylactic Percutaneous Endoscopic Gastrostomy (PEG) Tube Placement and Use in Head and Neck Patients Following Intensity-Modulated Radiation Therapy (IMRT) Treatment: Concordance, Discrepancies, and the Role of Gabapentin.

PubMed

Yang, Wuyang; McNutt, Todd R; Dudley, Sara A; Kumar, Rachit; Starmer, Heather M; Gourin, Christine G; Moore, Joseph A; Evans, Kimberly; Allen, Mysha; Agrawal, Nishant; Richmon, Jeremy D; Chung, Christine H; Quon, Harry

2016-04-01

The prophylactic placement of a percutaneous endoscopic gastrostomy (PEG) tube in the head and neck cancer (HNC) patient is controversial. We sought to identify factors associated with prophylactic PEG placement and actual PEG use. Since 2010, data regarding PEG placement and use were prospectively recorded in a departmental database from January 2010 to December 2012. HNC patients treated with intensity-modulated radiation therapy (IMRT) were retrospectively evaluated from 2010 to 2012. Variables potentially associated with patient post-radiation dysphagia from previous literature, and our experience was evaluated. We performed multivariate logistic regression on these variables with PEG placement and PEG use, respectively, to compare the difference of association between the two arms. We identified 192 HNC patients treated with IMRT. Prophylactic PEG placement occurred in 121 (63.0 %) patients, with PEG use in 97 (80.2 %) patients. PEG placement was associated with male gender (p < .01), N stage ≥ N2 (p < .05), pretreatment swallowing difficulties (p < .01), concurrent chemotherapy (p < .01), pretreatment KPS ≥80 (p = .01), and previous surgery (p = .02). Concurrent chemotherapy (p = .03) was positively associated with the use of PEG feeding by the patient, whereas pretreatment KPS ≥80 (p = .03) and prophylactic gabapentin use (p < .01) were negatively associated with PEG use. The analysis suggests there were discrepancies between prophylactic PEG tube placement and actual use. Favorable pretreatment KPS, no pretreatment dysphagia, no concurrent chemotherapy, and the use of gabapentin were significantly associated with reduced PEG use. This analysis may help refine the indications for prophylactic PEG placement.

Colonoscopy Preparation: Polyethylene Glycol with Gatorade is as Safe and Efficacious as 4 Liters of Polyethylene Glycol with Balanced Electrolytes

PubMed Central

McKenna, Thomas; Macgill, Alice; Porat, Gail; Friedenberg, Frank K.

2013-01-01

Background Four liters of polyethylene glycol 3350 with balanced electrolytes for colonoscopy preparation has had poor acceptance. Another approach is the use of electrolyte-free PEG combined with 1.9L of Gatorade. Despite its widespread use, there are no data on metabolic safety and minimal data on efficacy. Our aim was to assess the efficacy and electrolyte safety of these two PEG-based preparations. Methods This was a prospective, randomized, single-blind, non-inferiority trial. Patients were randomized to 238g PEG + 1.9L Gatorade or 4L of PEG-ELS containing 236g PEG. Split dosing was not performed. On procedure day blood was drawn for basic chemistries. The primary outcome was preparation quality from procedure photos using the Boston Bowel Preparation Scale. Results We randomized 136 patients (66 PEG + Gatorade, 70 PEG-ELS). There were no differences in preparation scores between the two agents in the ITT analysis (7.2 ± 1.9 for PEG-ELS and 7.0 ± 2.1 for PEG + Gatorade; p = 0.45). BBPS scores were identical for those who completed the preparation and dietary instructions as directed (7.4 ± 1.7 for PEG-ELS, and 7.4 ± 1.8 for PEG + Gatorade; p = 0.98). There were no statistical differences in serum electrolytes between the two preparations. Patients who received PEG + Gatorade gave higher overall satisfaction scores for the preparation experience (p = 0.001), and had fewer adverse effects. Conclusions Use of 238g PEG + 1.9L Gatorade appears to be safe, better tolerated, and non-inferior to 4L PEG-ELS. This preparation may be especially useful for patients who previously tolerated PEG-ELS poorly. PMID:22711499

Directed aggregation of carbon nanotube on curved surfaces by polymer induced depletion attraction

NASA Astrophysics Data System (ADS)

Lee, Hsin-Chieh; Jiang, Hong-Ren

2017-12-01

In this study, we show that by chemically grafting macromolecule, polyethylene glycol (PEG), onto CNTs, PEG-CNTs become dispersible in an aqueous solution with tunable depletion interactions with each other. The aggregation of the PEG-CNTs can be controlled by adding PEG polymers into the solution. PEG-CNTs not only aggregate with each other but also tend to aggregate on curved surfaces. Due to this property, we show that PEG-CNTs can be directed to aggregate on particles and patterned surfaces. Depletion interaction induced aggregation of PEG-CNTs may provide a method to place PEG-CNTs on a specific position for different applications ranging from biomedical to industrial usages.

They can interact, but can they learn? Toddlers' transfer learning from touchscreens and television.

PubMed

Moser, Alecia; Zimmermann, Laura; Dickerson, Kelly; Grenell, Amanda; Barr, Rachel; Gerhardstein, Peter

2015-09-01

Despite the ubiquity of touchscreen applications and television programs for young children, developmental research suggests that learning in this context is degraded relative to face-to-face interactions. Most previous research has been limited to transfer of learning from videos, making it difficult to isolate the relative perceptual and social influences for transfer difficulty, and has not examined whether the transfer deficit persists across early childhood when task complexity increases. The current study examined whether the transfer deficit persists in older children using a complex puzzle imitation task constructed to investigate transfer from video demonstrations. The current test adapted this task to permit bidirectional transfer from touchscreens as well. To test for bidirectional transfer deficits, 2.5- and 3-year-olds were shown how to assemble a three-piece puzzle on either a three-dimensional magnetic board or a two-dimensional touchscreen (Experiment 1). Unidirectional transfer from video was also tested (Experiment 2). Results indicate that a bidirectional transfer deficit persists through 3 years, with younger children showing a greater transfer deficit; despite high perceptual similarities and social engagement, children learned less in transfer tasks, supporting the memory flexibility account of the transfer deficit. Implications of these findings for use of screen media (e.g., video, tablets) in early education are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy

PubMed Central

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-01-01

AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy. PMID:24044042

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

PubMed

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-09-16

To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy.

Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(epsilon-caprolactone) and poly(ethylene glycol) macromer.

PubMed

Cho, C S; Han, S Y; Ha, J H; Kim, S H; Lim, D Y

1999-04-30

Poly(ethylene glycol)(PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(epsilon-caprolactone)(PCL) and PEG macromer were synthesized to obtain a bioerodible hydrogel. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature (Tg) and melting temperature (Tm) of PEG networks and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of clonazepam (CNZ) released from the SIPNs increased with higher content in the SIPNs, lower drug loading, lower concentration of PEG macromer during the SIPNs preparation, and higher molecular weight of PEG. In particular, a combination with low PEG content and low CNZ solubility in water led to long-term constant release from these matrices in vitro and in vivo. Copyright.

Design-based science and the transfer of science knowledge and real-world problem-solving skills

NASA Astrophysics Data System (ADS)

Fortus, David Leon

Design-Based Science (DBS) helps students develop new scientific knowledge and problem-solving skills in the context of designing artifacts. This pedagogy was developed as a response to the potential problem of transfer of knowledge from academic settings to extra classroom environments. This dissertation describes DBS in detail and attempts to answer three questions: (1) Do DBS curricula support students' efforts to transfer newly constructed science knowledge and 'designerly' skills (Baynes, 1994) to the solution of new real-world design problems in an extra-classroom setting? (2) Do DBS curricula support students' efforts to construct new scientific knowledge? (3) Do DBS curricula support students' efforts to develop 'designerly' problem-solving skills? Ninety-two students attending a public high school serving a working class community participated in the consecutive enactments of three different DBS units over one school year. The analysis of pre- and posttests and of artifacts created by the students demonstrated that substantial knowledge was constructed during each of the enactments, with the tests leading to effect sizes of 2.1 on the first unit, 1.9 on the second, and 2.7 on the third. After each enactment the students solved a new design problem as a transfer task. The transfer tasks were unsequestered, unsupported by the teacher, lasted three days, were done in the school's library, required new learning, and were solved in groups of four. In order to generate an individual measure of transfer, the students responded to an individual post-transfer written test after each transfer task was completed, that assessed their understanding and recollection of the solution their group submitted. For all three units there was a stronger correlation between the individual transfer scores and posttests scores than with pretest scores, indicating that the knowledge and skills that were constructed during the enactments supported the solution of the transfer tasks. The correlations with the posttests increased from one enactment to the next, demonstrating that the students' transfer performance improved as they gained more experience in DBS classrooms. Potential threats to the study's internal validity that were identified and discussed were improved teacher proficiency, the nature of the transfer tasks, the difficulty of the science content covered by the units, the similarity between the units and the transfer tasks, and the similarity between the transfer tasks. This dissertation demonstrates that: (a) appropriate learning environments can foster transfer, (b) transfer performance can improve over time, and (c) that it may be necessary to rethink and redefine the procedures for identifying and assessing real-world transfer.

Identification of Poly(ethylene glycol) and Poly(ethylene glycol)-Based Detergents Using Peptide Search Engines.

PubMed

Ahmadi, Shiva; Winter, Dominic

2018-06-05

Poly(ethylene glycol) (PEG) is one of the most common polymer contaminations in mass spectrometry (MS) samples. At present, the detection of PEG and other polymers relies largely on manual inspection of raw data, which is laborious and frequently difficult due to sample complexity and retention characteristics of polymer species in reversed-phase chromatography. We developed a new strategy for the automated identification of PEG molecules from tandem mass spectrometry (MS/MS) data using protein identification algorithms in combination with a database containing "PEG-proteins". Through definition of variable modifications, we extend the approach for the identification of commonly used PEG-based detergents. We exemplify the identification of different types of polymers by static nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS) analysis of pure detergent solutions and data analysis using Mascot. Analysis of liquid chromatography-tandem mass spectrometry (LC-MS/MS) runs of a PEG-contaminated sample by Mascot identified 806 PEG spectra originating from four PEG species using a defined set of modifications covering PEG and common PEG-based detergents. Further characterization of the sample for unidentified PEG species using error-tolerant and mass-tolerant searches resulted in identification of 3409 and 3187 PEG-related MS/MS spectra, respectively. We further demonstrate the applicability of the strategy for Protein Pilot and MaxQuant.

Plasma-mediated grafting of poly(ethylene glycol) on polyamide and polyester surfaces and evaluation of antifouling ability of modified substrates.

PubMed

Dong, Baiyan; Jiang, Hongquan; Manolache, Sorin; Wong, Amy C Lee; Denes, Ferencz S

2007-06-19

A simple cold plasma technique was developed to functionalize the surfaces of polyamide (PA) and polyester (PET) for the grafting of polyethylene glycol (PEG) with the aim of reducing biofilm formation. The surfaces of PA and PET were treated with silicon tetrachloride (SiCl4) plasma, and PEG was grafted onto plasma-functionalized substrates (PA-PEG, PET-PEG). Different molecular weights of PEG and grafting times were tested to obtain optimal surface coverage by PEG as monitored by electron spectroscopy for chemical analysis (ESCA). The presence of a predominant C-O peak on the PEG-modified substrates indicated that the grafting was successful. Data from hydroxyl group derivatization and water contact angle measurement also indicated the presence of PEG after grafting. The PEG-grafted PA and PET under optimal conditions had similar chemical composition and hydrophilicity; however, different morphology changes were observed after grafting. Both PA-PEG and PET-PEG surfaces developed under optimal plasma conditions showed about 96% reduction in biofilm formation by Listeria monocytogenes compared with that of the corresponding unmodified substrates. This plasma functionalization method provided an efficient way to graft PEG onto PA and PET surfaces. Because of the high reactivity of Si-Cl species, this method could potentially be applied to other polymeric materials.

Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

PubMed

Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

2015-01-01

Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

Polyethylene glycol-coated blue-emitting silicon dots with improved properties for uses in aqueous and biological environments

NASA Astrophysics Data System (ADS)

Rodríguez Sartori, Damián; Lillo, Cristian R.; Romero, Juan J.; Dell‧Arciprete, María Laura; Miñán, Alejandro; de Mele, Mónica Fernández Lorenzo; Gonzalez, Mónica C.

2016-11-01

Grafting of polyethylene glycol (PEG) to ultrasmall photoluminescent silicon dots (SiDs) is expected to improve and expand the applications of these particles to aqueous environments and biological systems. Herein we report a novel one-pot synthesis of robust, highly water compatible PEG-coated SiDs (denoted as PEG-SiDs) of (3.3 ± 0.5) nm size. The nanoparticles’ synthesis is based on the liquid phase oxidation of magnesium silicide using PEG as reaction media and leading to high PEG density grafting. PEG-SiDs enhanced photophysical, photosensitising, and solution properties in aqueous environments are described and compared to those of 2 nm size PEG-coated SiDs with low PEG density grafting (denoted as PEG-NHSiDs) obtained from a multistep synthesis strategy. PEG-SiDs form highly dispersed suspensions in water showing stable photoluminescence and quantum yields of Φ = 0.13 ± 0.04 at 370 nm excitation in air-saturated suspensions. These particles exhibited the capacity of photosensitising the formation of singlet molecular oxygen, not observed for PEG-NHSiDs. PEG robust shielding of the silicon core luminescent properties is further demonstrated in bio-imaging experiments stressing the strong interaction between PEG-SiDs and Staphylococcus aureus smears by observing the photoluminescence of particles. PEG-SiDs were found to be nontoxic to S. aureus cells at concentrations of 100 mg ml-1, though a bacteriostatic effect on S. aureus biofilms was observed upon UV-A irradiation under conditions where light alone has no effect.

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells.

PubMed

Yan, Jinyin; Song, Bo; Hu, Wanning; Meng, Ying; Niu, Fengling; Han, Xiaochen; Ge, Yuhui; Li, Ning

2018-05-01

Doxorubicin (DOX) can be used to treat malignant tumors, but with multiple adverse effects. Graphene oxide-polyethylene glycol (GO-PEG) is a novel nanoscale carrier material and can elevate solubility and biocompatibility of drugs. This study prepared a GO-PEG-DOX complex, whose toxicity and antitumor effects were evaluated on mouse EMT-6 breast cancer cells. GO-PEG-DOX complex was prepared for calculating the drug carrier rate of DOX on GO-PEG by MV approach. EMT-6 cells were treated with 40 μg/mL GO-PEG, 1 μg/mL DOX, or 40 μg/mL +1 μg/mL GO-PEG-DOX for 72 h of incubation. Cells without treatment were considered the control group. Cell survival rate and apoptotic rate were tested at different time points. GO-PEG and GO-PEG-DOX complex were successfully prepared with satisfactory solubility. After 72 h of incubation, EMT-6 cells after GO-PEG-DOX treatment had significantly higher survival rate than GO-PEG group (p < 0.05). All three treatment groups had significantly elevated apoptotic rates than control group (p < 0.05). GO-PEG-DOX group had much more apoptosis (p < 0.05 compared with DOX group). Moreover, with elongated treatment time, all groups showed decreased survival rate (p < 0.05). GO-PEG did not reduce the cytotoxicity of DOX on EMT-6 cells. GO-PEG-DOX complex can increase the water solubility and targeting sensitivity of DOX, with facilitating effects on DOX-induced tumor cell apoptosis.

Randomised clinical trial: Polyethylene glycol 3350 with sports drink vs. polyethylene glycol with electrolyte solution as purgatives for colonoscopy--the incidence of hyponatraemia.

PubMed

Matro, R; Daskalakis, C; Negoianu, D; Katz, L; Henry, C; Share, M; Kastenberg, D

2014-09-01

Polyethylene glycol 3350 plus sports drink (PEG-SD) is a hypo-osmotic purgative commonly used for colonoscopy, though little safety data are available. To evaluate the effect of PEG-SD on serum sodium (Na) and other electrolytes compared with PEG-electrolyte solution (PEG-ELS). We performed a single center, prospective, randomised, investigator-blind comparison of PEG-ELS to PEG-SD in out-patients undergoing colonoscopy. Laboratories were obtained at baseline and immediately before and after colonoscopy. The primary endpoint was development of hyponatraemia (Na <135 mmol/L) the day of colonoscopy. Changes in electrolyte levels were computed as the difference between the lowest value on the day of colonoscopy and baseline. Purgative tolerance and efficacy were assessed. A total of 389 patients were randomised; 364 took purgative and had baseline and day of colonoscopy labs (180 PEG-SD, 184 PEG-ELS). The groups were well matched except for a higher fraction of women and Blacks in PEG-ELS. Seven patients (3.9%) in PEG-SD and four patients (2.2%) in PEG-ELS developed hyponatraemia (OR = 1.82, 95% CI: 0.45-8.62, P = 0.376). Changes in electrolytes from baseline were small but significantly worse with PEG-SD for sodium, potassium and chloride (P = 0.001, 0.012, 0.001, respectively). Preparation completion, adverse events, and overall colon cleansing were similar between the groups, but PEG-ELS had more excellent preparations (52% vs. 30%; P = 0.001). Greater, but very modest, electrolyte changes occur with PEG-SD. Hyponatraemia is infrequent with both purgatives. A significant increase in hyponatraemia was not identified for PEG-SD vs. PEG-ELS, but the sample size may have been inadequate to identify a small, but clinically important difference. ClinicalTrials.gov identifier NCT01299779. © 2014 John Wiley & Sons Ltd.

Intermanual transfer and bilateral cortical plasticity is maintained in older adults after skilled motor training with simple and complex tasks

PubMed Central

Dickins, Daina S. E.; Sale, Martin V.; Kamke, Marc R.

2015-01-01

Intermanual transfer refers to the phenomenon whereby unilateral motor training induces performance gains in both the trained limb and in the opposite, untrained limb. Evidence indicates that intermanual transfer is attenuated in older adults following training on a simple ballistic movement task, but not after training on a complex task. This study investigated whether differences in plasticity in bilateral motor cortices underlie these differential intermanual transfer effects in older adults. Twenty young (<35 years-old) and older adults (>65 years) trained on a simple (repeated ballistic thumb abduction) and complex (sequential finger-thumb opposition) task in separate sessions. Behavioral performance was used to quantify intermanual transfer between the dominant (trained) and non-dominant (untrained) hands. The amplitude of motor-evoked potentials induced by single pulse transcranial magnetic stimulation was used to investigate excitability changes in bilateral motor cortices. Contrary to predictions, both age groups exhibited performance improvements in both hands after unilateral skilled motor training with simple and complex tasks. These performance gains were accompanied by bilateral increases in cortical excitability in both groups for the simple but not the complex task. The findings suggest that advancing age does not necessarily influence the capacity for intermanual transfer after training with the dominant hand. PMID:25999856

Activation of the prefrontal cortex while performing a task at preferred slow pace and metronome slow pace: a functional near-infrared spectroscopy study.

PubMed

Shimoda, Kaori; Moriguchi, Yoshiya; Tsuchiya, Kenji; Katsuyama, Shiori; Tozato, Fusae

2014-01-01

Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions.

Rapid Transfer of Abstract Rules to Novel Contexts in Human Lateral Prefrontal Cortex

PubMed Central

Cole, Michael W.; Etzel, Joset A.; Zacks, Jeffrey M.; Schneider, Walter; Braver, Todd S.

2011-01-01

Flexible, adaptive behavior is thought to rely on abstract rule representations within lateral prefrontal cortex (LPFC), yet it remains unclear how these representations provide such flexibility. We recently demonstrated that humans can learn complex novel tasks in seconds. Here we hypothesized that this impressive mental flexibility may be possible due to rapid transfer of practiced rule representations within LPFC to novel task contexts. We tested this hypothesis using functional MRI and multivariate pattern analysis, classifying LPFC activity patterns across 64 tasks. Classifiers trained to identify abstract rules based on practiced task activity patterns successfully generalized to novel tasks. This suggests humans can transfer practiced rule representations within LPFC to rapidly learn new tasks, facilitating cognitive performance in novel circumstances. PMID:22125519

Comparison of polyethylene glycol with and without electrolytes in the treatment of constipation in elderly institutionalized patients: a randomized, double-blind, parallel-group study.

PubMed

Seinelä, Lauri; Sairanen, Ulla; Laine, Tarmo; Kurl, Sangita; Pettersson, Tiina; Happonen, Pertti

2009-01-01

Polyethylene glycol (PEG) is a commonly used osmotic laxative. PEG with electrolytes is mixed with water, but PEG without electrolytes can also be mixed with, for example, juice, coffee or tea, making it more palatable. Laxatives, including PEG, are commonly used by the elderly, particularly those living in institutions. Few clinical studies, however, have investigated the use of PEG in this population. To test whether PEG 4000 without electrolytes (hypotonic PEG) is at least as effective and safe as PEG 4000 with electrolytes (isotonic PEG) in elderly institutionalized constipated patients. The acceptability of the treatments was also compared. This randomized, double-blind, parallel-group study was conducted at ten private assisted-living facilities or communal nursing homes in Finland. Eligible patients were required to have used isotonic PEG at a stable dose without any other treatment for constipation (except for Plantago ovata seeds) for at least 2 weeks prior to a run-in period. After the 1-week run-in, 62 patients (mean age 86 years; range 66-99 years) were randomly either switched to receive hypotonic PEG or continued to receive isotonic PEG, both dissolved in water, 12 g once or twice daily or once every other day, for 4 weeks. Stool frequency, stool consistency, stool straining and gastrointestinal symptoms were recorded. Safety laboratory tests were conducted before and after the treatment period. Acceptability was assessed at the end of the study. At week 4, mean (SD) weekly stool frequencies in the hypotonic and isotonic PEG groups were 8.5 (4.5) and 8.4 (3.6), respectively. The mean stool frequency ratio (95% CI) was 0.90 (0.74, 1.10); thus, the PEG products were considered equally effective. At week 4, the proportion of patients with soft or normal stool consistency was higher in the hypotonic PEG group than in the isotonic PEG group (70% vs 52%), but this difference was not statistically significant. There were no differences between the groups in stool straining or gastrointestinal symptoms. In the safety laboratory tests, no clinically significant differences between the groups were detected, although plasma sodium level was statistically significantly lower in the hypotonic PEG group at the end of the study (137.7 vs 138.9 mmol/L, respectively; p = 0.012). Most patients were willing to continue their study treatment (85% in the hypotonic PEG and 63% in the isotonic PEG group; p = 0.070). Compared with only 12% of the patients receiving hypotonic PEG, however, 31% of the patients in the isotonic PEG group rated the taste of the study treatment as bad or very bad (p = 0.101). Hypotonic PEG solution is as effective as isotonic PEG in the treatment of constipation in elderly institutionalized patients. Both treatments appear safe, well tolerated and, when dissolved in water, well accepted by the majority of the patients. When desired, switching from isotonic to hypotonic PEG can safely take place in elderly individuals without compromising efficacy.

Charge Transfer Between Quantum Dots and Peptide-Coupled Redox Complexes

DTIC Science & Technology

2009-01-01

labeled with reactive metal complexes includ- ing a ruthenium chelate (Ru), a bis-bipyridine ruthe- nium chelate (ruthenium-bpy), and a ferrocene metal...of unconjugated QDs and the metal complex–labeled peptides immobilized on indium tin oxide (ITO) electrodes. The ruthenium and ferrocene peptide...Ag/AgCI E v s. N H E E v s. v ac uu m (e V ) Ruthenium Ferrocene Ruthenium-bpy DHLA QDs DHLA-PEG QDs Quantum dot Metal complex CB VB E0X of QDs Fe

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles

NASA Astrophysics Data System (ADS)

Yamini, D.; Devanand Venkatasubbu, G.; Kumar, J.; Ramakrishnan, V.

2014-01-01

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass.

Use of amphiphilic triblock copolymers for enhancing removal efficiency of organic pollutant from contaminated media

NASA Astrophysics Data System (ADS)

Lee, Jun Hyup; Lee, Byungsun; Son, Intae; Kim, Jae Hong; Kim, Chunho; Yoo, Ji Yong; Wu, Jong-Pyo; Kim, Younguk

2015-11-01

We have studied amphiphilic triblock copolymers poly(ethylene glycol)- b-poly(propylene glycol)- b-poly(ethylene glycol) (PEG- b-PPG- b-PEG) and poly(propylene glycol)- b-poly(ethylene glycol)- b-poly(propylene glycol) (PPG- b-PEG- b-PPG) as possible substitutes for sodium dodecyl sulfate as anionic surfactants for the removal of hydrophobic contaminants. The triblock copolymers were compared with sodium dodecyl sulfate in terms of their abilities to remove toluene as hydrophobic contaminant in fuel, and the effects of polymer structure, PEG content, and concentration were studied. The PEG- b-PPG- b-PEG copolymer containing two hydrophilic PEG blocks was more effective for the removal of hydrophobic contaminant at extremely high concentration. We also measured the removal capabilities of the triblock copolymers having various PEG contents and confirmed that removal capability was greatest at 10% PEG content regardless of polymer structure. As with sodium dodecyl sulfate, the removal efficiency of a copolymer has a positive correlation with its concentration. Finally, we proposed the amphiphilic triblock copolymer of PPG- b-PEG- b-PPG bearing 10% PEG content that proved to be the most effective substitute for sodium dodecyl sulfate.

Lamellar, micro-phase separated blends of methyl cellulose and dendritic polyethylene glycol, POSS-PEG.

PubMed

Chinnam, Parameswara Rao; Mantravadi, Ramya; Jimenez, Jayvic C; Dikin, Dmitriy A; Wunder, Stephanie L

2016-01-20

Blends of methyl cellulose (MC) and liquid pegylated polyoctahedralsilsesquioxane (POSS-PEG) were prepared from non-gelled, aqueous solutions at room temperature (RT), which was below their gel temperatures (Tm). Lamellar, fibrillated films (pure MC) and increasingly micro-porous morphologies with increasing POSS-PEG content were formed, which had RT moduli between 1 and 5GPa. Evidence of distinct micro-phase separated MC and POSS-PEG domains was indicated by the persistence of the MC and POSS-PEG (at 77K) crystal structures in the X-ray diffraction data, and scanning transmission electron images. Mixing of MC and POSS-PEG in the interface region was indicated by suppression of crystallinity in the POSS-PEG, and increases/decreases in the glass transition temperatures (Tg) of POSS-PEG/MC in the blends compared with the pure components. These interface interactions may serve as cross-link sites between the micro-phase separated domains that permit incorporation of high amounts of POSS-PEG in the blends, prevent macro-phase separation and result in rubbery material properties (at high POSS-PEG content). Above Tg/Tm of POSS-PEG, the moduli of the blends increase with MC content as expected. However, below Tg/Tm of POSS-PEG, the moduli are greater for blends with high POSS-PEG content, suggesting that it behaves like semi-crystalline polyethylene oxide reinforced with silica (SiO1.5). Copyright © 2015 Elsevier Ltd. All rights reserved.

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

PubMed

Ma, Guilei; Zhang, Chao; Zhang, Linhua; Sun, Hongfan; Song, Cunxian; Wang, Chun; Kong, Deling

2016-01-01

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo.

PubMed

Du, Xiao-Jiao; Wang, Ji-Long; Liu, Wei-Wei; Yang, Jin-Xian; Sun, Chun-Yang; Sun, Rong; Li, Hong-Jun; Shen, Song; Luo, Ying-Li; Ye, Xiao-Dong; Zhu, Yan-Hua; Yang, Xian-Zhu; Wang, Jun

2015-11-01

Poly(ethylene glycol) (PEG) is usually used to protect nanoparticles from rapid clearance in blood. The effects are highly dependent on the surface PEG density of nanoparticles. However, there lacks a detailed and informative study in PEG density and in vivo drug delivery due to the critical techniques to precisely control the surface PEG density when maintaining other nano-properties. Here, we regulated the polymeric nanoparticles' size and surface PEG density by incorporating poly(ε-caprolactone) (PCL) homopolymer into poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) and adjusting the mass ratio of PCL to PEG-PCL during the nanoparticles preparation. We further developed a library of polymeric nanoparticles with different but controllable sizes and surface PEG densities by changing the molecular weight of the PCL block in PEG-PCL and tuning the molar ratio of repeating units of PCL (CL) to that of PEG (EG). We thus obtained a group of nanoparticles with variable surface PEG densities but with other nano-properties identical, and investigated the effects of surface PEG densities on the biological behaviors of nanoparticles in mice. We found that, high surface PEG density made the nanoparticles resistant to absorption of serum protein and uptake by macrophages, leading to a greater accumulation of nanoparticles in tumor tissue, which recuperated the defects of decreased internalization by tumor cells, resulting in superior antitumor efficacy when carrying docetaxel. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

PubMed Central

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp)8, has a strong affinity to bone surface. The aim of this study was to synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp)8-PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp)8-PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone. PMID:28507436

Single endoscopist-performed percutaneous endoscopic gastrostomy tube placement.

PubMed

Erdogan, Askin

2013-07-14

To investigate whether single endoscopist-performed percutaneous endoscopic gastrostomy (PEG) is safe and to compare the complications of PEG with those reported in the literature. Patients who underwent PEG placement between June 2001 and August 2011 at the Baskent University Alanya Teaching and Research Center were evaluated retrospectively. Patients whose PEG was placed for the first time by a single endoscopist were enrolled in the study. PEG was performed using the pull method. All of the patients were evaluated for their indications for PEG, major and minor complications resulting from PEG, nutritional status, C-reactive protein (CRP) levels and the use of antibiotic treatment or antibiotic prophylaxis prior to PEG. Comorbidities, rates, time and reasons for mortality were also evaluated. The reasons for PEG removal and PEG duration were also investigated. Sixty-two patients underwent the PEG procedure for the first time during this study. Eight patients who underwent PEG placement by 2 endoscopists were not enrolled in the study. A total of 54 patients were investigated. The patients' mean age was 69.9 years. The most common indication for PEG was cerebral infarct, which occurred in approximately two-thirds of the patients. The mean albumin level was 3.04 ± 0.7 g/dL, and 76.2% of the patients' albumin levels were below the normal values. The mean CRP level was high in 90.6% of patients prior to the procedure. Approximately two-thirds of the patients received antibiotics for either prophylaxis or treatment for infections prior to the PEG procedure. Mortality was not related to the procedure in any of the patients. Buried bumper syndrome was the only major complication, and it occurred in the third year. In such case, the PEG was removed and a new PEG tube was placed via surgery. Eight patients (15.1%) experienced minor complications, 6 (11.1%) of which were wound infections. All wound infections except one recovered with antibiotic treatment. Two patients had bleeding from the PEG site, one was resolved with primary suturing and the other with fresh frozen plasma transfusion. The incidence of major and minor complications is in keeping with literature. This finding may be noteworthy, especially in developing countries.

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone.

PubMed

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10-800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

Dynamic, continuous multitasking training leads to task-specific improvements but does not transfer across action selection tasks

NASA Astrophysics Data System (ADS)

Bender, Angela D.; Filmer, Hannah L.; Naughtin, Claire K.; Dux, Paul E.

2017-12-01

The ability to perform multiple tasks concurrently is an ever-increasing requirement in our information-rich world. Despite this, multitasking typically compromises performance due to the processing limitations associated with cognitive control and decision-making. While intensive dual-task training is known to improve multitasking performance, only limited evidence suggests that training-related performance benefits can transfer to untrained tasks that share overlapping processes. In the real world, however, coordinating and selecting several responses within close temporal proximity will often occur in high-interference environments. Over the last decade, there have been notable reports that training on video action games that require dynamic multitasking in a demanding environment can lead to transfer effects on aspects of cognition such as attention and working memory. Here, we asked whether continuous and dynamic multitasking training extends benefits to tasks that are theoretically related to the trained tasks. To examine this issue, we asked a group of participants to train on a combined continuous visuomotor tracking task and a perceptual discrimination task for six sessions, while an active control group practiced the component tasks in isolation. A battery of tests measuring response selection, response inhibition, and spatial attention was administered before and immediately after training to investigate transfer. Multitasking training resulted in substantial, task-specific gains in dual-task ability, but there was no evidence that these benefits generalized to other action control tasks. The findings suggest that training on a combined visuomotor tracking and discrimination task results in task-specific benefits but provides no additional value for untrained action selection tasks.

Structural integrity of callosal midbody influences intermanual transfer in a motor reaction-time task.

PubMed

Bonzano, Laura; Tacchino, Andrea; Roccatagliata, Luca; Mancardi, Giovanni Luigi; Abbruzzese, Giovanni; Bove, Marco

2011-02-01

Training one hand on a motor task results in performance improvements in the other hand, also when stimuli are randomly presented (nonspecific transfer). Corpus callosum (CC) is the main structure involved in interhemispheric information transfer; CC pathology occurs in patients with multiple sclerosis (PwMS) and is related to altered performance of tasks requiring interhemispheric transfer of sensorimotor information. To investigate the role of CC in nonspecific transfer during a pure motor reaction-time task, we combined motor behavior with diffusion tensor imaging analysis in PwMS. Twenty-two PwMS and 10 controls, all right-handed, were asked to respond to random stimuli with appropriate finger opposition movements with the right (learning) and then the left (transfer) hand. PwMS were able to improve motor performance reducing response times with practice with a trend similar to controls and preserved the ability to transfer the acquired motor information from the learning to the transfer hand. A higher variability in the transfer process, indicated by a significantly larger standard deviation of mean nonspecific transfer, was found in the PwMS group with respect to the control group, suggesting the presence of subtle impairments in interhemispheric communication in some patients. Then, we correlated the amount of nonspecific transfer with mean fractional anisotropy (FA) values, indicative of microstructural damage, obtained in five CC subregions identified on PwMS's FA maps. A significant correlation was found only in the subregion including posterior midbody (Pearson's r = 0.74, P = 0.003), which thus seems to be essential for the interhemispheric transfer of information related to pure sensorimotor tasks. Copyright © 2010 Wiley-Liss, Inc.

Safety analysis of patient transfers and handling tasks.

PubMed

Vieira, Er; Kumar, S

2009-10-01

Low-back disorders are related to biomechanical demands, and nurses are among the professionals with the highest rates. Quantification of risk factors is important for safety assessment and reduction of low-back disorders. This study aimed to quantify physical demands of frequent nursing tasks and provide evidence-based recommendations to increase low-back safety. Thirty-six volunteer female nurses participated in a cross-sectional study of nine nursing tasks. Lumbar range of motion (ROM) and motion during nursing tasks were measured. Compression and shear forces at L5/S1, ligament strain and percentage of population without sufficient torso strength to perform 14 phases of nine nursing tasks were estimated. Peak flexions during trolley-to-bed, bed-to-chair and chair-to-bed transfers reached the maximum flexion ROM of the nurses. Average lumbar flexion during trolley-to-bed transfers was >50% of flexion ROM, being higher than during all other tasks. Mean (SD) compression at L5/S1 (4754 N (437 N)) and population without sufficient torso strength (37% (9%)) were highest during the pushing phase of bed-to-trolley transfers. Shear force (487 N (40 N)) and ligament strain (14% (5%)) were highest during the pulling phase of trolley-to-bed transfers. Nursing tasks impose high biomechanical demands on the lumbar spine. Excessive lumbar flexion and forces are critical aspects of manual transfers requiring most of the nurses' capabilities. Evidence-based recommendations to improve low-back safety in common nursing tasks were provided. Fitness to work, job modifications and training programs can now be designed and assessed based on the results.

Comparative Performance in Single-Port Versus Multiport Minimally Invasive Surgery, and Small Versus Large Operative Working Spaces: A Preclinical Randomized Crossover Trial.

PubMed

Marcus, Hani J; Seneci, Carlo A; Hughes-Hallett, Archie; Cundy, Thomas P; Nandi, Dipankar; Yang, Guang-Zhong; Darzi, Ara

2016-04-01

Surgical approaches such as transanal endoscopic microsurgery, which utilize small operative working spaces, and are necessarily single-port, are particularly demanding with standard instruments and have not been widely adopted. The aim of this study was to compare simultaneously surgical performance in single-port versus multiport approaches, and small versus large working spaces. Ten novice, 4 intermediate, and 1 expert surgeons were recruited from a university hospital. A preclinical randomized crossover study design was implemented, comparing performance under the following conditions: (1) multiport approach and large working space, (2) multiport approach and intermediate working space, (3) single-port approach and large working space, (4) single-port approach and intermediate working space, and (5) single-port approach and small working space. In each case, participants performed a peg transfer and pattern cutting tasks, and each task repetition was scored. Intermediate and expert surgeons performed significantly better than novices in all conditions (P < .05). Performance in single-port surgery was significantly worse than multiport surgery (P < .01). In multiport surgery, there was a nonsignificant trend toward worsened performance in the intermediate versus large working space. In single-port surgery, there was a converse trend; performances in the intermediate and small working spaces were significantly better than in the large working space. Single-port approaches were significantly more technically challenging than multiport approaches, possibly reflecting loss of instrument triangulation. Surprisingly, in single-port approaches, in which triangulation was no longer a factor, performance in large working spaces was worse than in intermediate and small working spaces. © The Author(s) 2015.

The role of tactile feedback in grip force during laparoscopic training tasks.

PubMed

Wottawa, Christopher R; Cohen, Jeremiah R; Fan, Richard E; Bisley, James W; Culjat, Martin O; Grundfest, Warren S; Dutson, Erik P

2013-04-01

Laparoscopic minimally invasive surgery has revolutionized surgical care by reducing trauma to the patient, thereby decreasing the need for medication and shortening recovery times. During open procedures, surgeons can directly feel tissue characteristics. However, in laparoscopic surgery, tactile feedback during grip is attenuated and limited to the resistance felt in the tool handle. Excessive grip force during laparoscopic surgery can lead to tissue damage. Providing additional supplementary tactile feedback may allow subjects to have better control of grip force and identification of tissue characteristics, potentially decreasing the learning curve associated with complex minimally invasive techniques. A tactile feedback system has been developed and integrated into a modified laparoscopic grasper that allows forces applied at the grasper tips to be felt by the surgeon's hands. In this study, 15 subjects (11 novices, 4 experts) were asked to perform single-handed peg transfers using these laparoscopic graspers in three trials (feedback OFF, ON, OFF). Peak and average grip forces (newtons) during each grip event were measured and compared using a Wilcoxon ranked test in which each subject served as his or her own control. After activating the tactile feedback system, the novice subject population showed significant decreases in grip force (p < 0.003). When the system was deactivated for the third trial, there were significant increases in grip force (p < 0.003). Expert subjects showed no significant improvements with the addition of tactile feedback (p > 0.05 in all cases). Supplementary tactile feedback helped novice subjects reduce grip force during the laparoscopic training task but did not offer improvements for the four expert subjects. This indicates that tactile feedback may be beneficial for laparoscopic training but has limited long-term use in the nonrobotic setting.

Validity evidence for the Fundamentals of Laparoscopic Surgery (FLS) program as an assessment tool: a systematic review.

PubMed

Zendejas, Benjamin; Ruparel, Raaj K; Cook, David A

2016-02-01

The Fundamentals of Laparoscopic Surgery (FLS) program uses five simulation stations (peg transfer, precision cutting, loop ligation, and suturing with extracorporeal and intracorporeal knot tying) to teach and assess laparoscopic surgery skills. We sought to summarize evidence regarding the validity of scores from the FLS assessment. We systematically searched for studies evaluating the FLS as an assessment tool (last search update February 26, 2013). We classified validity evidence using the currently standard validity framework (content, response process, internal structure, relations with other variables, and consequences). From a pool of 11,628 studies, we identified 23 studies reporting validity evidence for FLS scores. Studies involved residents (n = 19), practicing physicians (n = 17), and medical students (n = 8), in specialties of general (n = 17), gynecologic (n = 4), urologic (n = 1), and veterinary (n = 1) surgery. Evidence was most common in the form of relations with other variables (n = 22, most often expert-novice differences). Only three studies reported internal structure evidence (inter-rater or inter-station reliability), two studies reported content evidence (i.e., derivation of assessment elements), and three studies reported consequences evidence (definition of pass/fail thresholds). Evidence nearly always supported the validity of FLS total scores. However, the loop ligation task lacks discriminatory ability. Validity evidence confirms expected relations with other variables and acceptable inter-rater reliability, but other validity evidence is sparse. Given the high-stakes use of this assessment (required for board eligibility), we suggest that more validity evidence is required, especially to support its content (selection of tasks and scoring rubric) and the consequences (favorable and unfavorable impact) of assessment.

Transfer of training between distinct motor tasks after stroke: implications for task-specific approaches to upper-extremity neurorehabilitation.

PubMed

Schaefer, Sydney Y; Patterson, Chavelle B; Lang, Catherine E

2013-09-01

Although task-specific training is emerging as a viable approach for recovering motor function after stroke, there is little evidence for whether the effects of such training transfer to other functional motor tasks not directly practiced in therapy. The purpose of the current study was to test whether training on one motor task in individuals with chronic hemiparesis poststroke would transfer to untrained tasks that were either spatiotemporally similar or different. In all, 11 participants with chronic mild to moderate hemiparesis following stroke completed 5 days of supervised massed practice of a feeding task with their affected side. Performance on the feeding task, along with 2 other untrained functional upper-extremity motor tasks (sorting, dressing) was assessed before and after training. Performance of all 3 tasks improved significantly after training exclusively on 1 motor task. The amount of improvement in the untrained tasks was comparable and was not dependent on the degree of similarity to the trained task. Because the number and type of tasks that can be practiced are often limited within standard stroke rehabilitation, results from this study will be useful for designing task-specific training plans to maximize therapy benefits.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

PubMed Central

Kim, NaJung; Jiang, Dahai; Jacobi, Ashley; Lennox, Kim A.; Rose, Scott; Behlke, Mark A.; Salem, Aliasger K.

2011-01-01

Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for research and treatment of numerous diseases. In this study, we develop and characterize a delivery system for siRNA composed of polyethylenimine (PEI), polyethylene glycol (PEG), and mannose (Man). Cationic PEI complexes and compacts siRNA, PEG forms a hydrophilic layer outside of the polyplex for steric stabilization, and mannose serves as a cell binding ligand for macrophages. The PEI-PEG-mannose delivery system was constructed in two different ways. In the first approach, mannose and PEG chains are directly conjugated to the PEI backbone. In the second approach, mannose is conjugated to one end of the PEG chain and the other end of the PEG chain is conjugated to the PEI backbone. The PEI-PEG-mannose delivery systems were synthesized with 3.45 – 13.3 PEG chains and 4.7 – 3.0 mannose molecules per PEI. The PEI-PEG-Man-siRNA polyplexes displayed a coarse surface in Scanning Electron Microscopy (SEM) images. Polyplex sizes were found to range from 169nm to 357nm. Gel retardation assays showed that the PEI-PEG-mannose polymers are able to efficiently complex with siRNA at low N/P ratios. Confocal microscope images showed that the PEI-PEG-Man-siRNA polyplexes could enter cells and localized in the lysosomes at 2 hours post-incubation. Pegylation of the PEI reduced toxicity without any adverse reduction in knockdown efficiency relative to PEI alone. Mannosylation of the PEI-PEG could be carried out without any significant reduction in knockdown efficiency relative to PEI alone. Conjugating mannose to PEI via the PEG spacer generated superior toxicity and gene knockdown activity relative to conjugating mannose and PEG directly onto the PEI backbone. PMID:21864664

Affinity partitioning of human antibodies in aqueous two-phase systems.

PubMed

Rosa, P A J; Azevedo, A M; Ferreira, I F; de Vries, J; Korporaal, R; Verhoef, H J; Visser, T J; Aires-Barros, M R

2007-08-24

The partitioning of human immunoglobulin (IgG) in a polymer-polymer and polymer-salt aqueous two-phase system (ATPS) in the presence of several functionalised polyethylene glycols (PEGs) was studied. As a first approach, the partition studies were performed with pure IgG using systems in which the target protein remained in the bottom phase when the non-functionalised systems were tested. The effect of increasing functionalised PEG concentration and the type of ligand were studied. Afterwards, selectivity studies were performed with the most successful ligands first by using systems containing pure proteins and an artificial mixture of proteins and, subsequently, with systems containing a Chinese hamster ovary (CHO) cells supernatant. The PEG/phosphate ATPS was not suitable for the affinity partitioning of IgG. In the PEG/dextran ATPS, the diglutaric acid functionalised PEGs (PEG-COOH) displayed great affinity to IgG, and all IgG could be recovered in the top phase when 20% (w/w) of PEG 150-COOH and 40% (w/w) PEG 3350-COOH were used. The selectivity of these functionalised PEGs was evaluated using an artificial mixture of proteins, and PEG 3350-COOH did not show affinity to IgG in the presence of typical serum proteins such as human serum albumin and myoglobin, while in systems with PEG 150-COOH, IgG could be recovered with a yield of 91%. The best purification of IgG from the CHO cells supernatant was then achieved in a PEG/dextran ATPS in the presence of PEG 150-COOH with a recovery yield of 93%, a purification factor of 1.9 and a selectivity to IgG of 11. When this functionalised PEG was added to the ATPS, a 60-fold increase in selectivity was observed when compared to the non-functionalised systems.

Microencapsulation of islets within alginate/poly(ethylene glycol) gels cross-linked via Staudinger ligation

PubMed Central

Hall, Kristina K.; Gattás-Asfura, Kerim M.; Stabler, Cherie L.

2010-01-01

Functionalized alginate and PEG polymers were used to generate covalently linked alginate-PEG (XAlgPEG) microbeads of high stability. The cell-compatible Staudinger ligation scheme was used to chemoselectively cross-link phosphine-terminated poly(ethylene glycol) (PEG) to azide-functionalized alginate, resulting in XAlgPEG hydrogels. XAlgPEG microbeads were formed by co-incubation of the two polymers, followed by ionic cross-linking of the alginate using barium ions. The enhanced stability and gel properties of the resulting XAlgPEG microbeads, as well as the compatibility of these polymers for the encapsulation of islets and beta cells lines, were investigated. Our data show that XAlgPEG microbeads exhibit superior resistance to osmotic swelling compared to traditional barium cross-linked alginate (Ba-Alg) beads, with a 5-fold reduction in observed swelling, as well as resistance to dissolution via chelation solution. Diffusion and porosity studies found XAlgPEG beads to exhibit properties comparable to standard Ba-Alg. Our data found XAlgPEG microbeads to be highly cell compatible with insulinoma cell lines, as well as rat and human pancreatic islets, where the viability and functional assessment of cells within XAlgPEG were comparable to Ba-Alg controls. The remarkable improved stability, as well as demonstrated cellular compatibility, of XAlgPEG hydrogels makes them an appealing option for a wide variety of tissue engineering applications. PMID:20654745

Polyethylene glycol as marker for nitrofurazone allergy: 20 years of experience from Turkey.

PubMed

Özkaya, Esen; Kılıç, Sıla

2018-03-01

Polyethylene glycols (PEGs) and propylene glycol (PG) are used as vehicles in various medicinal and cosmetic products. They are potential contact sensitizers, including low molecular weight PEGs in nitrofurazone preparations that are still widely used in Turkey. To investigate the prevalence of allergic contact dermatitis caused by PEG and PG in a relatively large group of patients in Turkey. In this retrospective, cross-sectional, single-centre study, 836 patients patch tested with PEG and PG between 1996 and 2015 were reviewed. Thirty-five patients (4.2%) showed positive patch test reactions to PEG, and 7 (0.8%) showed positive patch test reactions to PG, partly as late positive reactions with PEG. PEG sensitivity was almost exclusively related to nitrofurazone allergy. Patch test reactions to PG were currently relevant mainly with regard to the use of minoxidil, and antiherpetic or corticosteroid creams. Ten patients (25%) had concomitant contact allergies to various topical drugs containing mainly PEGs. PEG sensitivity seems to be a marker for contact allergy to topical nitrofurazone in Turkey. Nitrofurazone allergy appears to favour concomitant sensitization to PEG. We would suggest the inclusion of PEG in an extended baseline patch test series in Turkey. Late patch test readings are important to diagnose delayed positive reactions to PEG. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of Polyethylene Glycol-Electrolyte Solution vs Polyethylene Glycol-3350 for the Treatment of Fecal Impaction in Pediatric Patients

PubMed Central

Boles, Erin E.; Gaines, Cameryn L.

2015-01-01

OBJECTIVES: The objective of this study was to evaluate the safety and efficacy of polyethylene glycol-electrolyte solution vs polyethylene glycol-3350 for the treatment of fecal impaction in pediatric patients. METHODS: A retrospective, observational, institutional review board–approved study was conducted over a 1-year time period. Patients were included in the study if they were admitted to the hospital with a diagnosis of fecal impaction or constipation and were treated with either polyethylene glycol-electrolyte solution (PEG-ES) or polyethylene glycol-3350 (PEG-3350). Patients were excluded if they were discharged prior to resolution of treatment and/or did not receive PEG-ES or PEG-3350. RESULTS: Fifty-one patients (ranging in age from 1 month to 15 years) were evaluated: 23 patients received PEG-ES and 28 patients received PEG-3350. Sex, race, age, and weight were not statistically different between the 2 groups. Resolution of fecal impaction was not significantly different between PEG-ES vs PEG-3350 (87% and 86%, respectively; p = 0.87). There was only 1 reported side effect with PEG-3350, vs 11 reported side effects with PEG-ES (p < 0.01). CONCLUSIONS: Theses results suggest that PEG-3350 is as effective as PEG-ES for the treatment of fecal impaction in pediatric patients and is associated with fewer side effects. PMID:26170773

Comparison of Polyethylene Glycol-Electrolyte Solution vs Polyethylene Glycol-3350 for the Treatment of Fecal Impaction in Pediatric Patients.

PubMed

Boles, Erin E; Gaines, Cameryn L; Tillman, Emma M

2015-01-01

The objective of this study was to evaluate the safety and efficacy of polyethylene glycol-electrolyte solution vs polyethylene glycol-3350 for the treatment of fecal impaction in pediatric patients. A retrospective, observational, institutional review board-approved study was conducted over a 1-year time period. Patients were included in the study if they were admitted to the hospital with a diagnosis of fecal impaction or constipation and were treated with either polyethylene glycol-electrolyte solution (PEG-ES) or polyethylene glycol-3350 (PEG-3350). Patients were excluded if they were discharged prior to resolution of treatment and/or did not receive PEG-ES or PEG-3350. Fifty-one patients (ranging in age from 1 month to 15 years) were evaluated: 23 patients received PEG-ES and 28 patients received PEG-3350. Sex, race, age, and weight were not statistically different between the 2 groups. Resolution of fecal impaction was not significantly different between PEG-ES vs PEG-3350 (87% and 86%, respectively; p = 0.87). There was only 1 reported side effect with PEG-3350, vs 11 reported side effects with PEG-ES (p < 0.01). Theses results suggest that PEG-3350 is as effective as PEG-ES for the treatment of fecal impaction in pediatric patients and is associated with fewer side effects.

"Decisions, decisions, decisions": transfer and specificity of decision-making skill between sports.

PubMed

Causer, Joe; Ford, Paul R

2014-08-01

The concept of transfer of learning holds that previous practice or experience in one task or domain will enable successful performance in another related task or domain. In contrast, specificity of learning holds that previous practice or experience in one task or domain does not transfer to other related tasks or domains. The aim of the current study is to examine whether decision-making skill transfers between sports that share similar elements, or whether it is specific to a sport. Participants (n = 205) completed a video-based temporal occlusion decision-making test in which they were required to decide on which action to execute across a series of 4 versus 4 soccer game situations. A sport engagement questionnaire was used to identify 106 soccer players, 43 other invasion sport players and 58 other sport players. Positive transfer of decision-making skill occurred between soccer and other invasion sports, which are related and have similar elements, but not from volleyball, supporting the concept of transfer of learning.

Unsupervised Transfer Learning via Multi-Scale Convolutional Sparse Coding for Biomedical Applications

PubMed Central

Chang, Hang; Han, Ju; Zhong, Cheng; Snijders, Antoine M.; Mao, Jian-Hua

2017-01-01

The capabilities of (I) learning transferable knowledge across domains; and (II) fine-tuning the pre-learned base knowledge towards tasks with considerably smaller data scale are extremely important. Many of the existing transfer learning techniques are supervised approaches, among which deep learning has the demonstrated power of learning domain transferrable knowledge with large scale network trained on massive amounts of labeled data. However, in many biomedical tasks, both the data and the corresponding label can be very limited, where the unsupervised transfer learning capability is urgently needed. In this paper, we proposed a novel multi-scale convolutional sparse coding (MSCSC) method, that (I) automatically learns filter banks at different scales in a joint fashion with enforced scale-specificity of learned patterns; and (II) provides an unsupervised solution for learning transferable base knowledge and fine-tuning it towards target tasks. Extensive experimental evaluation of MSCSC demonstrates the effectiveness of the proposed MSCSC in both regular and transfer learning tasks in various biomedical domains. PMID:28129148

Working memory training and transfer in older adults.

PubMed

Richmond, Lauren L; Morrison, Alexandra B; Chein, Jason M; Olson, Ingrid R

2011-12-01

There has been a great deal of interest, both privately and commercially, in using working memory training exercises to improve general cognitive function. However, many of the laboratory findings for older adults, a group in which this training is of utmost interest, are discouraging due to the lack of transfer to other tasks and skills. Importantly, improvements in everyday functioning remain largely unexamined in relation to WM training. We trained working memory in older adults using a task that encourages transfer in young adults (Chein & Morrison, 2010). We tested transfer to measures of working memory (e.g., Reading Span), everyday cognitive functioning [the Test of Everyday Attention (TEA) and the California Verbal Learning Test (CVLT)], and other tasks of interest. Relative to controls, trained participants showed transfer improvements in Reading Span and the number of repetitions on the CVLT. Training group participants were also significantly more likely to self-report improvements in everyday attention. Our findings support the use of ecological tasks as a measure of transfer in an older adult population.

Template optimization and transfer in perceptual learning.

PubMed

Kurki, Ilmari; Hyvärinen, Aapo; Saarinen, Jussi

2016-08-01

We studied how learning changes the processing of a low-level Gabor stimulus, using a classification-image method (psychophysical reverse correlation) and a task where observers discriminated between slight differences in the phase (relative alignment) of a target Gabor in visual noise. The method estimates the internal "template" that describes how the visual system weights the input information for decisions. One popular idea has been that learning makes the template more like an ideal Bayesian weighting; however, the evidence has been indirect. We used a new regression technique to directly estimate the template weight change and to test whether the direction of reweighting is significantly different from an optimal learning strategy. The subjects trained the task for six daily sessions, and we tested the transfer of training to a target in an orthogonal orientation. Strong learning and partial transfer were observed. We tested whether task precision (difficulty) had an effect on template change and transfer: Observers trained in either a high-precision (small, 60° phase difference) or a low-precision task (180°). Task precision did not have an effect on the amount of template change or transfer, suggesting that task precision per se does not determine whether learning generalizes. Classification images show that training made observers use more task-relevant features and unlearn some irrelevant features. The transfer templates resembled partially optimized versions of templates in training sessions. The template change direction resembles ideal learning significantly but not completely. The amount of template change was highly correlated with the amount of learning.

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles.

PubMed

Yamini, D; Devanand Venkatasubbu, G; Kumar, J; Ramakrishnan, V

2014-01-03

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass. Copyright © 2013 Elsevier B.V. All rights reserved.

The effects of aging on the asymmetry of inter-limb transfer in a visuomotor task.

PubMed

Pan, Zhujun; Van Gemmert, Arend W A

2013-09-01

The direction of the asymmetry of inter-limb transfer has been suggested to identify the specialization of each hemisphere when performing a motor task. In an earlier study, we showed that trajectory information is only transferred from the right to the left hand, while final movement outcome-associated parameters transferred in both directions when right-hand-dominant individuals perform a motor task with visual distorted feedback. In the current study, we try to replicate this finding in young adults and test whether the asymmetry of inter-limb transfer in visuomotor task reduces in older adults, suggesting that hemispheric lateralization reduces with age. Young and older adults (all right-hand-dominant) performed a multidirectional point-to-point drawing task in which the visual feedback was rotated and the gain was increased. Half of the participants in each age group trained with the right hand and the other half trained with the left hand. Performances of both hands with non-distorted and distorted visual feedback were collected from all participants before and after the training session. The results showed that the pattern of inter-limb transfer was similar between young and older adults, i.e., inter-limb transfer is asymmetric for initial direction and symmetric for movement time and trajectory length. The results suggest that older adults retain the specialized functions of the non-dominant (right) hemisphere allowing them to program movement direction of a graphic aiming task when visual feedback is distorted.

Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis.

PubMed

Alvarez, Guillermo Cabrera; Madrid-Marina, Vicente; Jimenez-Mendez, Ricardo; Buitimea, Angel Leon; Román, Margarita Bahena; Cortez-Gomez, Rudyard; Esparza, Jorge Reyes; Rodríguez-Fragoso, Lourdes

2007-01-01

The aim of this study was to investigate the effects of combinations of pegilated-interferon (PEG-IFN), ribavirin, and danazol on thrombocytopenia and liver injury in rats with fibrosis. Male adult Wistar rats were treated with either mineral oil, danazol (0.83 mg/kg per day), PEG-interferon alpha-2a (PEG-IFN, 0.3 microg/ week) + ribavirin (12 mg/kg per day), PEG-IFN + ribavirin + danazol, CCl(4) (4 g/kg for eight weeks), CCl(4) + PEG-IFN + ribavirin, or CCl(4) + PEG-IFN + ribavirin+ danazol. The following assays were conducted: hematology, clinical chemistry, liver function, liver fibrosis, lymphocyte cytokine mRNA expression, and bone-marrow DNA content. Platelet counts were low in sham-treated animals and animals treated with PEG- IFN + ribavirin (30% and 25% respectively; P < 0.05). PEG-IFN + ribavirin + danazol reduced platelet counts of fibrotic animals by only 9% (P < 0.05). PEG- IFN + ribavirin reduced hepatic collagen content by 50%, whereas danazol + PEG-IFN + ribavirin reduced hepatic collagen content by 60% (P < 0.05). PEG-IFN + ribavirin reduced the total bilirubin concentration by 27%, alanine amino transferase (ALT) activity by 75% and gamma-glutamyl transpeptidase (gamma-GTP) activity by 74% (P < 0.05). In contrast, danazol + PEG-IFN + ribavirin reduced total bilirubin levels by 61%, alkaline phosphatase activity by 45%, ALT activity by 76%, and gamma-GTP activity by 74% (P < 0.05). The only treatment that increased interleukin 10 (IL-10) mRNA in fibrotic rats was PEG-IFN + ribavirin. However, danazol + PEG-IFN + ribavirin reduced the expression of IL-6, IL-10, tumor necrosis factor alpha and transforming growth factor ss. Bone-marrow DNA content was not altered by any treatment. In conclusion, PEG-IFN + ribavirin + danazol could be a new therapeutic option for patients with liver injury, fibrosis, and thrombocytopenia.

Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study

PubMed Central

Kusano, Chika; Yamada, Nobuo; Kikuchi, Kenji; Hashimoto, Masaji; Gotoda, Takuji

2016-01-01

Background: There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient’s family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients’ families after PEG in Japan. Methods: We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient’s families to ask about their satisfaction with and thoughts about PEG. Results: The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients’ families. When asked, “Was performing PEG a good decision?”, 57.5% (182/316) of the patients’ families answered yes. Meanwhile, when patients’ family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. Conclusions: Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG. PMID:27313796

Working memory plasticity in old age: practice gain, transfer, and maintenance.

PubMed

Li, Shu-Chen; Schmiedek, Florian; Huxhold, Oliver; Röcke, Christina; Smith, Jacqui; Lindenberger, Ulman

2008-12-01

Adult age differences in cognitive plasticity have been studied less often in working memory than in episodic memory. The authors investigated the effects of extensive working memory practice on performance improvement, transfer, and short-term maintenance of practice gains and transfer effects. Adults age 20-30 years and 70-80 years practiced a spatial working memory task with 2 levels of processing demands across 45 days for about 15 min per day. In both age groups and relative to age-matched, no-contact control groups, we found (a) substantial performance gains on the practiced task, (b) near transfer to a more demanding spatial n-back task and to numerical n-back tasks, and (c) 3-month maintenance of practice gains and near transfer effects, with decrements relative to postpractice performance among older but not younger adults. No evidence was found for far transfer to complex span tasks. The authors discuss neuronal mechanisms underlying adult age differences and similarities in patterns of plasticity and conclude that the potential of deliberate working memory practice as a tool for improving cognition in old age merits further exploration. Copyright (c) 2009 APA, all rights reserved.

Acquisition, retention and transfer of simulated laparoscopic tasks using fNIR and a contextual interference paradigm.

PubMed

Shewokis, Patricia A; Shariff, Faiz U; Liu, Yichuan; Ayaz, Hasan; Castellanos, Andres; Lind, D Scott

2017-02-01

Using functional near infrared spectroscopy, a noninvasive, optical brain imaging tool that monitors changes in hemodynamics within the prefrontal cortex (PFC), we assessed performance and cognitive effort during the acquisition, retention and transfer of multiple simulated laparoscopic tasks by novice learners within a contextual interference paradigm. Third-year medical students (n = 10) were randomized to either a blocked or random practice schedule. Across 3 days, students performed 108 acquisition trials of 3 laparoscopic tasks on the LapSim ® simulator followed by delayed retention and transfer tests. Performance metrics (Global score, Total time) and hemodynamic responses (total hemoglobin (μm)) were assessed during skill acquisition, retention and transfer. All acquisition tasks resulted in significant practice schedule X trial block interactions for the left medial anterior PFC. During retention and transfer, random performed the skills in less time and had lower total hemoglobin change in the right dorsolateral PFC than blocked. Compared with blocked, random practice resulted in enhanced learning through better performance and less cognitive load for retention and transfer of simulated laparoscopic tasks. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term effects of executive process training in young and old adults.

PubMed

Sandberg, Petra; Stigsdotter Neely, Anna

2016-10-01

Prior studies have examined the magnitude of training and transfer effects after process-based training in early and late adulthood. However, little is known about how long-lasting these effects are. Here we investigate the degree of stability of training gains and transfer effects in younger and older adults 18 months after completion of executive process training, tapping updating, inhibition, and shifting. From the original sample, 24 out of 30 older participants, and 19 out of 29 young adults, returned for follow-up assessment at which the criterion and transfer tests from pre- and post-test were re-administered. The results demonstrated stability of training gains in the updating criterion task (Letter Memory Running Span), and in a near transfer updating task (Number Memory Running Span) for both age groups. The young adults improved performance in two complex working memory tasks immediately after training. These transfer effects did not survive across time. Our results provide evidence that executive process training has its greatest effect on transfer tasks with a substantial process overlap with the trained tasks: only those effects are maintained over an 18 month period in both early and late adulthood.

The effect of bandwidth on telerobot system performance

NASA Technical Reports Server (NTRS)

Uebel, Mark; Ali, Michael S.; Minis, Ioannis

1991-01-01

The purpose of the experiment was to determine the effect that various slave-joint bandwidths have on telerobot system performance. The telerobot system consisted of a slave arm controlled by a master. The slave incorporated an impedance loop to provide local compliance in addition to the compliance provided by the operator via force feedback. Three joint bandwidths, 0.5, 1.0, and 2.0 Hz, were used. The performance measures were the task completion time and the sums of the squared forces and moments exerted on the environment. The task consisted of peg-in-hole insertion and removal. The results of the experiment indicate a significant performance decrease at 0.5-Hz bandwidth relative to the 1- and 2-Hz bandwidths. There was no significant change in performance between the 1- and 2-Hz bandwidths.

Steric and electrostatic surface forces on sulfonated PEG graft surfaces with selective albumin adsorption.

PubMed

Bremmell, Kristen E; Britcher, Leanne; Griesser, Hans J

2013-06-01

Addition of ionized terminal groups to PEG graft layers may cause additional interfacial forces to modulate the net interfacial interactions between PEG graft layers and proteins. In this study we investigated the effect of terminal sulfonate groups, characterizing PEG-aldehyde (PEG-CHO) and sulfonated PEG (PEG-SO3) graft layers by XPS and colloid probe AFM interaction force measurements as a function of ionic strength, in order to determine surface forces relevant to protein resistance and models of bio-interfacial interaction of such graft coatings. On the PEG-CHO surface the measured interaction force does not alter with ionic strength, typical of a repulsive steric barrier coating. An analogous repulsive interaction force of steric origin was also observed on the PEG-SO3 graft coating; however, the net interaction force changed with ionic strength. Interaction forces were modelled by steric and electrical double layer interaction theories, with fitting to a scaling theory model enabling determination of the spacing and stretching of the grafted chains. Albumin, fibrinogen, and lysozyme did not adsorb on the PEG-CHO coating, whereas the PEG graft with terminal sulfonate groups showed substantial adsorption of albumin but not fibrinogen or lysozyme from 0.15 M salt solutions. Under lower ionic strength conditions albumin adsorption was again minimized as a result of the increased electrical double-layer interaction observed with the PEG-SO3 modified surface. This unique and unexpected adsorption behaviour of albumin provides an alternative explanation to the "negative cilia" model used by others to rationalize observed thromboresistance on PEG-sulfonate coatings. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative analysis of polyethylene glycol (PEG) and PEGylated proteins in animal tissues by LC-MS/MS coupled with in-source CID.

PubMed

Gong, Jiachang; Gu, Xiaomei; Achanzar, William E; Chadwick, Kristina D; Gan, Jinping; Brock, Barry J; Kishnani, Narendra S; Humphreys, W Griff; Iyer, Ramaswamy A

2014-08-05

The covalent conjugation of polyethylene glycol (PEG, typical MW > 10k) to therapeutic peptides and proteins is a well-established approach to improve their pharmacokinetic properties and diminish the potential for immunogenicity. Even though PEG is generally considered biologically inert and safe in animals and humans, the slow clearance of large PEGs raises concerns about potential adverse effects resulting from PEG accumulation in tissues following chronic administration, particularly in the central nervous system. The key information relevant to the issue is the disposition and fate of the PEG moiety after repeated dosing with PEGylated proteins. Here, we report a novel quantitative method utilizing LC-MS/MS coupled with in-source CID that is highly selective and sensitive to PEG-related materials. Both (40K)PEG and a tool PEGylated protein (ATI-1072) underwent dissociation in the ionization source of mass spectrometer to generate a series of PEG-specific ions, which were subjected to further dissociation through conventional CID. To demonstrate the potential application of the method to assess PEG biodistribution following PEGylated protein administration, a single dose study of ATI-1072 was conducted in rats. Plasma and various tissues were collected, and the concentrations of both (40K)PEG and ATI-1072 were determined using the LC-MS/MS method. The presence of (40k)PEG in plasma and tissue homogenates suggests the degradation of PEGylated proteins after dose administration to rats, given that free PEG was absent in the dosing solution. The method enables further studies for a thorough characterization of disposition and fate of PEGylated proteins.

Transfer of skill engendered by complex task training under conditions of variable priority.

PubMed

Boot, Walter R; Basak, Chandramallika; Erickson, Kirk I; Neider, Mark; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Voss, Michelle W; Prakash, Ruchika; Lee, HyunKyu; Low, Kathy A; Kramer, Arthur F

2010-11-01

We explored the theoretical underpinnings of a commonly used training strategy by examining issues of training and transfer of skill in the context of a complex video game (Space Fortress, Donchin, 1989). Participants trained using one of two training regimens: Full Emphasis Training (FET) or Variable Priority Training (VPT). Transfer of training was assessed with a large battery of cognitive and psychomotor tasks ranging from basic laboratory paradigms measuring reasoning, memory, and attention to complex real-world simulations. Consistent with previous studies, VPT accelerated learning and maximized task mastery. However, the hypothesis that VPT would result in broader transfer of training received limited support. Rather, transfer was most evident in tasks that were most similar to the Space Fortress game itself. Results are discussed in terms of potential limitations of the VPT approach. Copyright © 2010 Elsevier B.V. All rights reserved.

Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-α (TNF-α) conjugate for therapeutic application.

PubMed

Dai, ChuanYun; Fu, Ya; Chen, ShaoCheng; Li, Biao; Yao, Bo; Liu, WanHong; Zhu, LiQing; Chen, Nan; Chen, Ji; Zhang, Qiang

2013-01-01

To design a releasable PEGylated TNF-α (rPEG-TNF-α), a cathepsin B-sensitive dipeptide (Val-Cit moiety) was inserted into conventional PEG-modified TNF-α (PEG-TNF-α), facilitating its clinical use for anti-tumor therapy. Comparative pharmacokinetic and pharmacodynamic studies showed that the half-lives of both PEGylated forms of TNF-α were ∼60-fold greater than that of unmodified TNF-α. In addition, the in vitro bioactivity of rPEG-TNF-α was greater than that of PEG-TNF-α with the same degree of PEG modification. Release of TNF-α from rPEG-TNF-α in vitro was dependent on the presence of cathepsin B and was inhibited by a cathepsin B inhibitor. Despite the potent cytotoxicity of unmodified TNF-α against normal cells, its PEGylated forms at higher TNF-α concentrations showed low cytotoxic activity against these cells. In contrast, both forms of PEGylated TNF-α showed potent cytotoxic activity against the B16 and L929 cell lines, with rPEG-TNF-α being 5- and 9-fold more potent, respectively, than PEG-TNF-α. Moreover, rPEG-TNF-α was a more potent in vivo antitumor agent than PEG-TNF-α.

The effects of oil-in-water nanoemulsion polyethylene glycol surface density on intracellular stability, pharmacokinetics, and biodistribution in tumor bearing mice.

PubMed

Hak, Sjoerd; Garaiova, Zuzana; Olsen, Linda Therese; Nilsen, Asbjørn Magne; de Lange Davies, Catharina

2015-04-01

Lipid-based nanoparticles are extensively studied for drug delivery. These nanoparticles are often surface-coated with polyethylene glycol (PEG) to improve their biodistribution. Until now, the effects of varying PEG surface density have been studied in a narrow and low range. Here, the effects of high and a broad range of PEG surface densities on the in vivo performance of lipid-based nanoparticles were studied. Oil-in-water nanoemulsions were prepared with PEG surface densities of 5-50 mol%. Confocal microscopy was used to assess intracellular disintegration in vitro. In vivo pharmacokinetics and biodistribution in tumor bearing mice were studied using a small animal optical imager. PEG surface density did not affect intracellular nanoemulsion stability. Surprisingly, circulation half-lives decreased with increasing PEG surface density. A plausible explanation was that nanoemulsion with high (50 mol%) PEG surface density activated the complement in a whole blood assay, whereas nanoemulsion with low (5 mol%) PEG density did not. In vivo, nanoemulsion with low PEG surface density was mostly confined to the tumor and organs of the mononuclear phagocyte system, whereas nanoemulsion with high PEG density accumulated throughout the mouse. Optimal PEG surface density of lipid-based nanoparticles for tumor targeting was found to be below 10 mol%.

Space Station Human Factors: Designing a Human-Robot Interface

NASA Technical Reports Server (NTRS)

Rochlis, Jennifer L.; Clarke, John Paul; Goza, S. Michael

2001-01-01

The experiments described in this paper are part of a larger joint MIT/NASA research effort and focus on the development of a methodology for designing and evaluating integrated interfaces for highly dexterous and multifunctional telerobot. Specifically, a telerobotic workstation is being designed for an Extravehicular Activity (EVA) anthropomorphic space station telerobot called Robonaut. Previous researchers have designed telerobotic workstations based upon performance of discrete subsets of tasks (for example, peg-in-hole, tracking, etc.) without regard for transitions that operators go through between tasks performed sequentially in the context of larger integrated tasks. The experiments presented here took an integrated approach to describing teleoperator performance and assessed how subjects operating a full-immersion telerobot perform during fine position and gross position tasks. In addition, a Robonaut simulation was also developed as part of this research effort, and experimentally tested against Robonaut itself to determine its utility. Results show that subject performance of teleoperated tasks using both Robonaut and the simulation are virtually identical, with no significant difference between the two. These results indicate that the simulation can be utilized as both a Robonaut training tool, and as a powerful design platform for telepresence displays and aids.

Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

PubMed

Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

2017-03-01

Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Lignin-based polyoxyethylene ether enhanced enzymatic hydrolysis of lignocelluloses by dispersing cellulase aggregates.

PubMed

Lin, Xuliang; Qiu, Xueqing; Yuan, Long; Li, Zihao; Lou, Hongming; Zhou, Mingsong; Yang, Dongjie

2015-06-01

Water-soluble lignin-based polyoxyethylene ether (EHL-PEG), prepared from enzymatic hydrolysis lignin (EHL) and polyethylene glycol (PEG1000), was used to improve enzymatic hydrolysis efficiency of corn stover. The glucose yield of corn stover at 72h was increased from 16.7% to 70.1% by EHL-PEG, while increase in yield with PEG4600 alone was 52.3%. With the increase of lignin content, EHL-PEG improved enzymatic hydrolysis of microcrystalline cellulose more obvious than PEG4600. EHL-PEG could reduce at least 88% of the adsorption of cellulase on the lignin film measured by quartz crystal microbalance with dissipation monitoring (QCM-D), while reduction with PEG4600 was 43%. Cellulase aggregated at 1220nm in acetate buffer analyzed by dynamic light scattering. EHL-PEG dispersed cellulase aggregates and formed smaller aggregates with cellulase, thereby, reduced significantly nonproductive adsorption of cellulase on lignin and enhanced enzymatic hydrolysis of lignocelluloses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates: Biophysical characterization and inclusion of lipophilic dietary supplements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koynova, Rumiana; Tihova, Mariana; Biopharma)

Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12) and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or oligolamellar liposomes in their liquid crystalline phase, in distinct difference from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar hysteretic phase behavior and can arrange into a long-living hexagonal phase at ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture with soy lecithin exchange lipids with the membranes much more actively than common lecithin liposomes; such an active lipid exchange might facilitate the discharging of the liposome cargo upon uptake and internalization, and can thus be important in drug delivery applications. Diacylglycerol-PEG lipidmore » liposome formulations can encapsulate up to 20-30 wt.% lipophilic dietary supplements such as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by way of dry mixing, avoiding the use of organic solvent.« less

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showedmore » efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal anti-PEG IgMs were generated against distinct PEGylated materials. • In vivo cross-reactivity to the immunized materials was limited. • Although in vitro cross-reactivity of generated monoclonal IgMs has been confirmed.« less

Single endoscopist-performed percutaneous endoscopic gastrostomy tube placement

PubMed Central

Erdogan, Askin

2013-01-01

AIM: To investigate whether single endoscopist-performed percutaneous endoscopic gastrostomy (PEG) is safe and to compare the complications of PEG with those reported in the literature. METHODS: Patients who underwent PEG placement between June 2001 and August 2011 at the Baskent University Alanya Teaching and Research Center were evaluated retrospectively. Patients whose PEG was placed for the first time by a single endoscopist were enrolled in the study. PEG was performed using the pull method. All of the patients were evaluated for their indications for PEG, major and minor complications resulting from PEG, nutritional status, C-reactive protein (CRP) levels and the use of antibiotic treatment or antibiotic prophylaxis prior to PEG. Comorbidities, rates, time and reasons for mortality were also evaluated. The reasons for PEG removal and PEG duration were also investigated. RESULTS: Sixty-two patients underwent the PEG procedure for the first time during this study. Eight patients who underwent PEG placement by 2 endoscopists were not enrolled in the study. A total of 54 patients were investigated. The patients’ mean age was 69.9 years. The most common indication for PEG was cerebral infarct, which occurred in approximately two-thirds of the patients. The mean albumin level was 3.04 ± 0.7 g/dL, and 76.2% of the patients’ albumin levels were below the normal values. The mean CRP level was high in 90.6% of patients prior to the procedure. Approximately two-thirds of the patients received antibiotics for either prophylaxis or treatment for infections prior to the PEG procedure. Mortality was not related to the procedure in any of the patients. Buried bumper syndrome was the only major complication, and it occurred in the third year. In such case, the PEG was removed and a new PEG tube was placed via surgery. Eight patients (15.1%) experienced minor complications, 6 (11.1%) of which were wound infections. All wound infections except one recovered with antibiotic treatment. Two patients had bleeding from the PEG site, one was resolved with primary suturing and the other with fresh frozen plasma transfusion. CONCLUSION: The incidence of major and minor complications is in keeping with literature. This finding may be noteworthy, especially in developing countries. PMID:23864780

Effects on violence of laws and policies facilitating the transfer of youth from the juvenile to the adult justice system: a report on recommendations of the Task Force on Community Preventive Services.

PubMed

Hahn, Robert; McGowan, Angela; Liberman, Akiva; Crosby, Alex; Fullilove, Mindy; Johnson, Robert; Moscicki, Eve; Price, LeShawndra; Snyder, Susan; Tuma, Farris; Lowy, Jessica; Briss, Peter; Cory, Stella; Stone, Glenda

2007-11-30

The independent, nonfederal Task Force on Community Preventive Services (Task Force), which directs the development of the Guide to Community Preventive Services (Community Guide), conducted a systematic review of published scientific evidence concerning the effectiveness of laws and policies that facilitate the transfer of juveniles to the adult criminal justice system to determine whether these transfers prevent or reduce violence among youth who have been transferred and among the juvenile population as a whole. For this review, transfer is defined as placing juveniles aged <18 years under the jurisdiction of the adult criminal justice system. The review followed Community Guide methods for conducting a systematic review of literature and for providing recommendations to public health decision makers. Available evidence indicates that transfer to the adult criminal justice system typically increases rather than decreases rates of violence among transferred youth. Available evidence was insufficient to determine the effect of transfer laws and policies on levels of violent crime in the overall juvenile population. On the basis of these findings, the Task Force recommends against laws or policies facilitating the transfer of juveniles to the adult criminal justice system for the purpose of reducing violence.

Rheological and thermal properties of polylactide/silicate nanocomposites films.

PubMed

Ahmed, Jasim; Varshney, Sunil K; Auras, Rafeal

2010-03-01

Polylactide (DL)/polyethylene glycol/silicate nanocomposite blended biodegradable films have been prepared by solvent casting method. Rheological and thermal properties were investigated for both neat amorphous polylactide (PLA-DL form) and blend of montmorillonite (clay) and poly (ethylene glycol) (PEG). Melt rheology of the PLA individually and blends (PLA/clay; PLA/PEG; PLA/PEG/clay) were performed by small amplitude oscillation shear (SAOS) measurement. Individually, PLA showed an improvement in the viscoelastic properties in the temperature range from 180 to 190 degrees C. Incorporation of nanoclay (3% to 9% wt) was attributed by significant improvements in the elastic modulus (G') of PLA/clay blend due to intercalation at higher temperature. Both dynamic modulii of PLA/PEG blend were significantly reduced with addition of 10% PEG. Rheometric measurement could not be conducted while PLA/PEG blends containing 25% PEG. A blend of PLA/PEG/clay (68/23/9) showed liquid-like properties with excellent flexibility. Thermal analysis of different clay loading films indicated that the glass transition temperatures (T(g)) remained unaffected irrespective of clay concentration due to immobilization of polymer chain in the clay nanocomposite. PEG incorporation reduced the T(g) of the blend (PLA/PEG and PLA/PEG/clay) significantly. Both rheological and thermal analysis data supported plasticization and flexibility of the blended films. It is also interesting to study competition between PLA and PEG for the intercalation into the interlayer spacing of the clay. This study indicates that PLA/montmorillonite blend could serve as effective nano-composite for packaging and other applications.

Systemic administration of a PEGylated adenovirus vector with a cancer-specific promoter is effective in a mouse model of metastasis.

PubMed

Yao, X; Yoshioka, Y; Morishige, T; Eto, Y; Watanabe, H; Okada, Y; Mizuguchi, H; Mukai, Y; Okada, N; Nakagawa, S

2009-12-01

Cancer gene therapy by adenovirus vectors (Advs) for metastatic cancer is limited because systemic administration of Adv produces low therapeutic effect and severe side effects. In this study, we generated a dual cancer-specific targeting vector system by using PEGylation and the telomere reverse transcriptase (TERT) promoter and attempted to treat experimental metastases through systemic administration of the vectors. We first optimized the molecular size of PEG and modification ratios used to create PEG-Ads. Systemic administration of PEG-Ad with 20-kDa PEG at a 45% modification ratio (PEG[20K/45%]-Ad) resulted in higher tumor-selective transgene expression than unmodified Adv. Next, we examined the effectiveness against metastases and side effects of a TERT promoter-driven PEG[20K/45%]-Ad containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk). Systemic administration of PEG-Ad-TERT/HSVtk showed superior antitumor effects against metastases with negligible side effects. A cytomegalovirus (CMV) promoter-driven PEG[20K/45%]-Ad also produced antimetastatic effects, but these were accompanied by side effects. Combining PEG-Ad-TERT/HSVtk with etoposide or 5-fluorouracil enhanced the therapeutic effects with negligible side effects. These results suggest that modification with 20-kDa PEG at a 45% modification ratio is the optimal condition for PEGylation of Adv, and PEG-Ad-TERT/HSVtk is a prototype Adv for systemic cancer gene therapy against metastases.

Physical characterization of polyethylene glycols by thermal analytical technique and the effect of humidity and molecular weight.

PubMed

Majumdar, R; Alexander, K S; Riga, A T

2010-05-01

Polyethylene glycols (PEGs) are well known as excipients in tablet dosage formulations. PEGs are generally known to be inert and have very few interactions with other components in the solid dosage forms. However, the physical nature of PEGs and how they affect the disintegration of tablets is not very well understood for the different molecular weights of PEGs. The knowledge of the effect of molecular weight of PEGs on their physical properties and the effect of humidity on the physical properties of PEGs are important parameters for the choice of a PEG to be acceptable as an excipient in pharmaceutical formulations. This study was done to determine the precision of the DSC physical properties for a wide range of PEGs with varying molecular weights from 194 to 23000 daltons. Nine different molecular weights of PEGs were examined in a DSC controlled Heat-Cool-Heat-Cool-Heat (HCHCH) cycle and the observed reproducible values of melting temperature, heat of fusion, crystallization temperature and the heat of crystallization were compared with values obtained from the literature and the observed percent crystallinity was again cross-checked by X-ray Diffraction (XRD) studies. The comparison values indicated acceptable precision. This study was also done to check the effect of humidity on the DSC physical properties for the entire range of PEGs. The results indicated that humidity probably has a higher effect on the physical properties of the low molecular weight PEGs as compared to the high molecular weight PEGs.

Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer

NASA Astrophysics Data System (ADS)

Zhang, Yumin; Yang, Cuihong; Wang, Weiwei; Liu, Jinjian; Liu, Qiang; Huang, Fan; Chu, Liping; Gao, Honglin; Li, Chen; Kong, Deling; Liu, Qian; Liu, Jianfeng

2016-02-01

Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.

Preparation before colonoscopy: a randomized controlled trial comparing different regimes.

PubMed

Jansen, Sita V; Goedhard, Jelle G; Winkens, Bjorn; van Deursen, Cees Th B M

2011-10-01

A good bowel preparation is essential for optimal visualization of the large intestine. Several preparations with a difference in composition and volume are available. We compared five methods for bowel cleansing quality and patients' acceptability. Adult ambulatory outpatients scheduled for elective colonoscopy were randomized to receive 4-l polyethylene glycol (PEG) solution (Klean-prep), 2-l PEG solution+ascorbic acid (Moviprep), or a sodium phosphate (NaP) solution, Phosphoral. Patients with the PEG solutions were also randomized to receive simethicone (Aeropax), to investigate whether this improves the bowel cleansing efficacy. Before colonoscopy patients completed a questionnaire about the acceptability and tolerability of the preparation. Endoscopists blinded to the type of preparation gave a bowel cleansing score. Data were available for 461 patients. 2-l PEG+ascorbic acid was noninferior to 4-l PEG in bowel cleansing quality of rectosigmoid and colon. NaP was noninferior to 4-l PEG in bowel cleansing quality of rectosigmoid but inferior for the whole colon. Compliance was significantly less in the group with 4-l PEG compared with the 2-l PEG and NaP group. No difference was found for abdominal cramps. Taste was significantly better in the 2-l PEG group. Simethicone did not improve the bowel cleansing quality. 2-l PEG+ascorbic acid was noninferior to the 4-l PEG solution in bowel cleansing quality and was better in taste and compliance. NaP was inferior to 4-l PEG in bowel cleansing quality. Addition of simethicone gave no improvement.

Impact of continuous training through distributed practice for acquisition of minimally invasive surgical skills.

PubMed

Nakata, Bruce Negrello; Cavalini, Worens; Bonin, Eduardo A; Salvalaggio, Paolo R; Loureiro, Marcelo P

2017-10-01

Minimally invasive surgery (MIS) requires the mastery of manual skills and a specific training is required. Apart from residencies and fellowships in MIS, other learning opportunities utilize massive training, mainly with use of simulators in short courses. A long-term postgraduate course represents an opportunity to learn through training using distributed practice. The objective of this study is to assess the use of distributed practice for acquisition of basic minimally invasive skills in surgeons who participated in a long-term MIS postgraduate course. A prospective, longitudinal and quantitative study was conducted among surgeons who attended a 1-year postgraduate course of MIS in Brazil, from 2012 to 2014. They were tested through five different exercises in box trainers (peg-transfer, passing, cutting, intracorporeal knot, and suture) in the first (t0), fourth (t1) and last, eighth, (t2) meetings of this course. The time and penalties of each exercise were collected for each participant. Participant skills were assessed based on time and accuracy on a previously tested score. Fifty-seven surgeons (participants) from three consecutive groups participated in this study. There was a significant improvement in scores in all exercises. The average increase in scores between t0 and t2 was 88% for peg-transfer, 174% for passing, 149% for cutting, 130% for intracorporeal knot, and 120% for suture (p < 0.001 for all exercises). Learning through distributed practice is effective and should be integrated into a MIS postgraduate course curriculum for acquisition of core skills.

RAFT-synthesized Graft Copolymers that Enhance pH-dependent Membrane Destabilization and Protein Circulation Times

PubMed Central

Crownover, Emily; Duvall, Craig L.; Convertine, Anthony; Hoffman, Allan S.; Stayton, Patrick S.

2012-01-01

Here we describe a new graft copolymer architecture of poly(propylacrylic acid) (polyPAA) that displays potent pH-dependent, membrane-destabilizing activity and in addition is shown to enhance protein blood circulation kinetics. PolyPAA containing a single telechelic alkyne functionality was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization with an alkyne-functional chain transfer agent (CTA) and coupled to RAFT polymerized poly(azidopropyl methacrylate) (polyAPMA) through azide-alkyne [3+2] Huisgen cycloaddition. The graft copolymers become membrane destabilizing at endosomal pH values and are active at significantly lower concentrations than the linear polyPAA. A biotin terminated polyPAA graft copolymer was prepared by grafting PAA onto polyAPMA polymerized with a biotin functional RAFT CTA. The blood circulation time and biodistribution of tritium labeled avidin conjugated to the polyPAA graft copolymer was characterized along with a clinically utilized 40 kDa branched polyethylene glycol (PEG) also possessing biotin functionalization. The linear and graft polyPAA increase the area under the curve (AUC) over avidin alone by 9 and 12 times, respectively. Furthermore, polyPAA graft copolymer conjugates accumulated in tumor tissue significantly more than the linear polyPAA and the branched PEG conjugates. The collective data presented in this report indicate that the polyPAA graft copolymers exhibit robust pH-dependent, membrane-destabilizing activity, low cytotoxicity and significantly enhance blood circulation time and tumor accumulation. PMID:21699931

PEG-asparaginase induced severe hypertriglyceridemia.

PubMed

Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

2016-04-01

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Chemical Interactions of Polyethylene Glycols (PEG) and Glycerol with Protein Functional Groups: Applications to PEG, Glycerol Effects on Protein Processes

PubMed Central

Knowles, DB; Shkel, Irina A; Phan, Noel M; Sternke, Matt; Lingeman, Emily; Cheng, Xian; Cheng, Lixue; O’Connor, Kevin; Record, M. Thomas

2015-01-01

Here we obtain the data needed to predict chemical interactions of polyethylene glycols (PEGs) and glycerol with proteins and related organic compounds, and thereby interpret or predict chemical effects of PEGs on protein processes. To accomplish this we determine interactions of glycerol and tetraEG with >30 model compounds displaying the major C, N, and O functional groups of proteins. Analysis of these data yields coefficients (α-values) quantifying interactions of glycerol, tetraEG and PEG end (-CH2OH) and interior (-CH2OCH2-) groups with these groups, relative to interactions with water. TetraEG (strongly) and glycerol (weakly) interact favorably with aromatic C, amide N, and cationic N, but unfavorably with amide O, carboxylate O and salt ions. Strongly unfavorable O and salt anion interactions help make both small and large PEGs effective protein precipitants. Interactions of tetraEG and PEG interior groups with aliphatic C are quite favorable, while interactions of glycerol and PEG end groups with aliphatic C are not. Hence tetraEG and PEG 300 favor unfolding of the DNA-binding domain of lac repressor (lacDBD) while glycerol, di- and mono-ethylene glycol are stabilizers. Favorable interactions with aromatic and aliphatic C explain why PEG400 greatly increases the solubility of aromatic hydrocarbons and steroids. PEG400-steroid interactions are unusually favorable, presumably because of simultaneous interactions of multiple PEG interior groups with the fused ring system of the steroid. Using α-values reported here, chemical contributions to PEG m-values can be predicted or interpreted in terms of changes in water-accessible surface area (ΔASA), and separated from excluded volume effects. PMID:25962980

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

PubMed

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bowel preparations for colonoscopy: an RCT.

PubMed

Di Nardo, Giovanni; Aloi, Marina; Cucchiara, Salvatore; Spada, Cristiano; Hassan, Cesare; Civitelli, Fortunata; Nuti, Federica; Ziparo, Chiara; Pession, Andrea; Lima, Mario; La Torre, Giuseppe; Oliva, Salvatore

2014-08-01

The ideal preparation regimen for pediatric colonoscopy remains elusive, and available preparations continue to represent a challenge for children. The aim of this study was to compare the efficacy, safety, tolerability, and acceptance of 4 methods of bowel cleansing before colonoscopy in children. This randomized, investigator-blinded, noninferiority trial enrolled all children aged 2 to 18 years undergoing elective colonoscopy in a referral center for pediatric gastroenterology. Patients were randomly assigned to receive polyethylene glycol (PEG) 4000 with simethicon (PEG-ELS group) or PEG-4000 with citrates and simethicone plus bisacodyl (PEG-CS+Bisacodyl group), or PEG 3350 with ascorbic acid (PEG-Asc group), or sodium picosulfate plus magnesium oxide and citric acid (NaPico+MgCit group). Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale. The primary end point was overall colon cleansing. Tolerability, acceptability, and compliance were also evaluated. Two hundred ninety-nine patients were randomly allocated to the 4 groups. In the per-protocol analysis, PEG-CS+Bisacodyl, PEG-Asc, and NaPico+MgCit were noninferior to PEG-ELS in bowel-cleansing efficacy of both the whole colon (P = .910) and colonic segments. No serious adverse events occurred in any group. Rates of tolerability, acceptability, and compliance were significantly higher in the NaPico+MgCit group. Low-volume PEG preparations (PEG-CS+Bisacodyl, PEG-Asc) and NaPico+MgCit are noninferior to PEG-ELS in children, representing an attractive alternative to high-volume regimens in clinical practice. Because of the higher tolerability and acceptability profile, NaPico+MgCit would appear as the most suitable regimen for bowel preparation in children. Copyright © 2014 by the American Academy of Pediatrics.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles.

PubMed

Hu, Tianmu; Qahtan, Anwar Saeed Ahmed; Lei, Lei; Lei, Zhixin; Zhao, Dapeng; Nie, Hemin

2018-03-01

In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p  > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.

Impact of large aggregated uricases and PEG diol on accelerated blood clearance of PEGylated canine uricase.

PubMed

Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

2012-01-01

Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. The size of conjugates is important for triggering such phenomena and we speculate that 40-60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase.

Impact of Large Aggregated Uricases and PEG Diol on Accelerated Blood Clearance of PEGylated Canine Uricase

PubMed Central

Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

2012-01-01

Background Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Methods and Findings Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. Conclusions The size of conjugates is important for triggering such phenomena and we speculate that 40–60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase. PMID:22745806

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

PubMed

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the treatment of chronic hepatitis C virus genotype 1 infection.

PubMed

Saab, S; Gordon, S C; Park, H; Sulkowski, M; Ahmed, A; Younossi, Z

2014-09-01

Sofosbuvir, an oral NS5B nucleotide polymerase inhibitor, is indicated for the treatment of patients infected with hepatitis C virus (HCV). To evaluate the long-term health economic outcomes of sofosbuvir + pegylated interferon alfa/ribavirin (pegIFN/RBV) compared with current treatments in patients infected with HCV genotype 1 in the US. A decision-analytic Markov model was developed to estimate health outcomes, number needed to treat and short-term and long-term economic outcomes, including incremental cost-effectiveness ratios and cost per sustained virological response (SVR), for several sofosbuvir-comparator regimen pairings for a cohort of 10 000 patients. It considered three patient cohorts: treatment-naïve, treatment-experienced and treatment-naïve human immunodeficiency virus (HIV) co-infected. Subgroup analyses were conducted for treatment-naïve patients with and without cirrhosis. Reductions in the incidence of new cases of liver-disease complications with sofosbuvir + pegIFN/RBV compared with pegIFN/RBV, boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV were 64-82%, 50-68%, 43-58% and 33-56%, respectively. Sofosbuvir + pegIFN/RBV was typically associated with the lowest 1-year cost per SVR. When considering the lifetime incremental cost per quality-adjusted life-year gained, sofosbuvir + pegIFN/RBV was the most cost-effective treatment option assessed. Sofosbuvir + pegIFN/RBV generally dominated (less costly and more effective than) boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV. Sofosbuvir + pegIFN/RBV yields more favourable future health and economic outcomes than current treatment regimens for patients across all levels of treatment experience and cirrhosis stage, as well as for individuals with or without HIV co-infection. © 2014 John Wiley & Sons Ltd.

Minority race and male sex as risk factors for non-beneficial gastrostomy tube placements after stroke.

PubMed

Faigle, Roland; Carrese, Joseph A; Cooper, Lisa A; Urrutia, Victor C; Gottesman, Rebecca F

2018-01-01

Percutaneous endoscopic gastrostomy (PEG) tubes are widely used for enteral feeding after stroke; however, PEG tubes placed in patients in whom death is imminent are considered non-beneficial. We sought to determine whether placement of non-beneficial PEG tubes differs by race and sex. In this retrospective cohort study, inpatient admissions for stroke patients who underwent palliative/withdrawal of care, were discharged to hospice, or died during the hospitalization, were identified from the Nationwide Inpatient Sample between 2007 and 2011. Logistic regression was used to evaluate the association between race and sex with PEG placement. Of 36,109 stroke admissions who underwent palliative/withdrawal of care, were discharge to hospice, or experienced in-hospital death, a PEG was placed in 2,258 (6.3%). Among PEG recipients 41.1% were of a race other than white, while only 22.0% of patients without PEG were of a minority race (p<0.001). The proportion of men was higher among those with compared to without a PEG tube (50.0% vs. 39.2%, p<0.001). Minority race was associated with PEG placement compared to whites (OR 1.75, 95% CI 1.57-1.96), and men had 1.27 times higher odds of PEG compared to women (95% CI 1.16-1.40). Racial differences were most pronounced among women: ethnic/racial minority women had over 2-fold higher odds of a PEG compared to their white counterparts (OR 2.09, 95% CI 1.81-2.41), while male ethnic/racial minority patients had 1.44 increased odds of a PEG when compared to white men (95% CI 1.24-1.67, p-value for interaction <0.001). Minority race and male sex are risk factors for non-beneficial PEG tube placements after stroke.

Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy.

PubMed

Kushwah, Varun; Katiyar, Sameer S; Agrawal, Ashish Kumar; Gupta, Ramesh C; Jain, Sanyog

2018-04-20

The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5-10μg/ml which self-assembled to form NPs with size 124.2±5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC (0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Copyright © 2018 Elsevier Inc. All rights reserved.

Earth orbital teleoperator manipulator system evaluation program

NASA Technical Reports Server (NTRS)

Brye, R. G.; Frederick, P. N.; Kirkpatrick, M., III; Shields, N. L., Jr.

1977-01-01

The operator's ability to perform five manipulator tip movements while using monoptic and stereoptic video systems was assessed. Test data obtained were compared with previous results to determine the impact of camera placement and stereoptic viewing on manipulator system performance. The tests were performed using the NASA MSFC extendible stiff arm Manipulator and an analog joystick controller. Two basic manipulator tasks were utilized. The minimum position change test required the operator to move the manipulator arm to touch a target contract. The dexterity test required removal and replacement of pegs.

Evaluation of ceiling lifts: transfer time, patient comfort and staff perceptions.

PubMed

Alamgir, Hasanat; Li, Olivia Wei; Yu, Shicheng; Gorman, Erin; Fast, Catherine; Kidd, Catherine

2009-09-01

Mechanical lifting devices have been developed to reduce healthcare worker injuries related to patient handling. The purpose of this study was to evaluate ceiling lifts in comparison to floor lifts based on transfer time, patient comfort and staff perceptions in three long-term care facilities with varying ceiling lift coverage. The time required to transfer or reposition patients along with patient comfort levels were recorded for 119 transfers. Transfers performed with ceiling lifts required on average less time (bed to chair transfers: 156.9 seconds for ceiling lift, 273.6 seconds for floor lift) and were found to be more comfortable for patients. In the three facilities, 143 healthcare workers were surveyed on their perceptions of patient handling tasks and equipment. For both transferring and repositioning tasks, staff preferred to use ceiling lifts and also found them to be less physically demanding. Further investigation is needed on repositioning tasks to ensure safe practice.

Interrelations between three fine motor skills in young adults.

PubMed

Lorås, Håvard; Sigmundsson, Hermundur

2012-08-01

Motor skills are typically considered to be highly specific, although some researchers have attempted to identify evidence for general motor aptitude. The present study tested these contentions by assessing the extent of relationship between fine motor tasks, using correlations between selected performance measures for three fine motor skills. University students ages 18 to 35 years (N = 305; 147 men, 158 women) completed three fine motor tasks with both right and left hands (placing pegs, posting coins, and placing bricks). Performance was assessed by time to complete each individual task. The intercorrelations between the three tasks were generally low and at a level that can be expected by chance (r < or = .3), indicating that performance was quite specific to the individual skills rather than attributable to a general ability. As a further test for evidence for a general motor ability, the dimensionality of the data set was analyzed using a principal component analysis on the correlation matrix. A three-factor solution explaining approximately 80% of the total variance in performance on the fine motor tasks was identified, where each factor could be associated with each fine motor task. These findings provide further support for the high specificity in fine motor skills and against the existence of a general aptitude for motor ability.

Transfer of training between distinct motor tasks after stroke: Implications for task- specific approaches to upper extremity neurorehabilitation

PubMed Central

Schaefer, Sydney Y.; Patterson, Chavelle B.; Lang, Catherine E.

2013-01-01

Background Although task-specific training is emerging as a viable approach for recovering motor function after stroke, there is little evidence for whether the effects of such training transfer to other functional motor tasks not directly practiced in therapy. Objective The purpose of the current study was to test whether training on one motor task would transfer to untrained tasks that were either spatiotemporally similar or different in individuals with chronic hemiparesis post-stroke. Methods Eleven participants with chronic mild-to-moderate hemiparesis following stroke completed five days of supervised massed practice of a feeding task with their affected side. Performance on the feeding task, along with two other untrained functional upper extremity motor tasks (sorting, dressing) was assessed before and after training. Results Performance of all three tasks improved significantly after training exclusively on one motor task. The amount of improvement in the untrained tasks was comparable, and was not dependent on the degree of similarity to the trained task. Conclusions Because the number and type of tasks that can be practiced are often limited within standard stroke rehabilitation, results from this study will be useful for designing task-specific training plans to maximize therapy benefits. PMID:23549521

On the temporal dynamics of spatial stimulus-response transfer between spatial incompatibility and Simon tasks

PubMed Central

Ivanoff, Jason; Blagdon, Ryan; Feener, Stefanie; McNeil, Melanie; Muir, Paul H.

2014-01-01

The Simon effect refers to the performance (response time and accuracy) advantage for responses that spatially correspond to the task-irrelevant location of a stimulus. It has been attributed to a natural tendency to respond toward the source of stimulation. When location is task-relevant, however, and responses are intentionally directed away (incompatible) or toward (compatible) the source of the stimulation, there is also an advantage for spatially compatible responses over spatially incompatible responses. Interestingly, a number of studies have demonstrated a reversed, or reduced, Simon effect following practice with a spatial incompatibility task. One interpretation of this finding is that practicing a spatial incompatibility task disables the natural tendency to respond toward stimuli. Here, the temporal dynamics of this stimulus-response (S-R) transfer were explored with speed-accuracy trade-offs (SATs). All experiments used the mixed-task paradigm in which Simon and spatial compatibility/incompatibility tasks were interleaved across blocks of trials. In general, bidirectional S-R transfer was observed: while the spatial incompatibility task had an influence on the Simon effect, the task-relevant S-R mapping of the Simon task also had a small impact on congruency effects within the spatial compatibility and incompatibility tasks. These effects were generally greater when the task contexts were similar. Moreover, the SAT analysis of performance in the Simon task demonstrated that the tendency to respond to the location of the stimulus was not eliminated because of the spatial incompatibility task. Rather, S-R transfer from the spatial incompatibility task appeared to partially mask the natural tendency to respond to the source of stimulation with a conflicting inclination to respond away from it. These findings support the use of SAT methodology to quantitatively describe rapid response tendencies. PMID:25191217

Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA:PEG ratios.

PubMed

Phan, Quoc Thong; Le, Mai Huong; Le, Thi Thu Huong; Tran, Thi Hong Ha; Xuan, Phuc Nguyen; Ha, Phuong Thu

2016-06-30

Targeting delivery system use natural drugs for tumor cells is an appealing platform help to reduce the side effects and enhance the therapeutic effects of the drug. In this study, we synthesized curcumin (Cur) loaded (D, L Poly lactic - Poly ethylenglycol) micelle (Cur/PLA-PEG) with the ratio of PLA/PEG of 3:1 2:1 1:1 1:2 and 1:3 (w/w) and another micelle modified by folate (Cur/PLA-PEG-Fol) for targeting cancer therapy. The PLA-PEG copolymer was synthesized by ring opening polymerization method. After loading onto the micelle, solubility of Cur increased from 0.38 to 0.73mgml(-1). The average size of prepared Cur/PLA-PEG micelles was from 60 to 69nm (corresponding to the ratio difference of PLA/PEG) and the drug encapsulating efficiency was from 48.8 to 91.3%. Compared with the Cur/PLA-PEG micelles, the size of Cur/PLA-PEG-Fol micelles were from 80 to 86nm and showed better in vitro cellular uptake and cytotoxicity towards HepG2 cells. The cytotoxicity of the NPs however depends much on the PEG component. The results demonstrated that Folate-modified micelles could serve as a potential nano carrier to improve solubility, anti-cancer activity of Cur and targeting ability of the system. Copyright © 2016 Elsevier B.V. All rights reserved.

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

NASA Astrophysics Data System (ADS)

Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

2017-06-01

Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule instability and slows polymerization rates at cell tips in a dynein-dependent manner

PubMed Central

Grallert, Agnes; Beuter, Christoph; Craven, Rachel A.; Bagley, Steve; Wilks, Deepti; Fleig, Ursula; Hagan, Iain M.

2006-01-01

The Schizosaccharomyces pombe CLIP170-associated protein (CLASP) Peg1 was identified in a screen for mutants with spindle formation defects and a screen for molecules that antagonized EB1 function. The conditional peg1.1 mutant enabled us to identify key features of Peg1 function. First, Peg1 was required to form a spindle and astral microtubules, yet destabilized interphase microtubules. Second, Peg1 was required to slow the polymerization rate of interphase microtubules that establish end-on contact with the cortex at cell tips. Third, Peg1 antagonized the action of S. pombe CLIP170 (Tip1) and EB1 (Mal3). Fourth, although Peg1 resembled higher eukaryotic CLASPs by physically associating with both Mal3 and Tip1, neither Tip1 nor Mal3 was required for Peg1 to destabilize interphase microtubules or for it to associate with microtubules. Conversely, neither Mal3 nor Tip1 required Peg1 to associate with microtubules or cell tips. Consistently, while mal3.Δ and tip1.Δ disrupted linear growth, corrupting peg1 + did not. Fifth, peg1.1 phenotypes resembled those arising from deletion of the single heavy or both light chains of fission yeast dynein. Furthermore, all interphase phenotypes arising from peg1 + manipulation relied on dynein function. Thus, the impact of S. pombe CLASP on interphase microtubule behavior is more closely aligned to dynein than EB1 or CLIP170. PMID:16951255

Transfer of motor and perceptual skills from basketball to darts

PubMed Central

Rienhoff, Rebecca; Hopwood, Melissa J.; Fischer, Lennart; Strauss, Bernd; Baker, Joseph; Schorer, Jörg

2013-01-01

The quiet eye is a perceptual skill associated with expertise and superior performance; however, little is known about the transfer of quiet eye across domains. We attempted to replicate previous skill-based differences in quiet eye and investigated whether transfer of motor and perceptual skills occurs between similar tasks. Throwing accuracy and quiet eye duration for skilled and less-skilled basketball players were examined in basketball free throw shooting and the transfer task of dart throwing. Skilled basketball players showed significantly higher throwing accuracy and longer quiet eye duration in the basketball free throw task compared to their less-skilled counterparts. Further, skilled basketball players showed positive transfer from basketball to dart throwing in accuracy but not in quiet eye duration. Our results raise interesting questions regarding the measurement of transfer between skills. PMID:24062703

Effect of the molecular structure of lignin-based polyoxyethylene ether on enzymatic hydrolysis efficiency and kinetics of lignocelluloses.

PubMed

Lin, Xuliang; Qiu, Xueqing; Zhu, Duming; Li, Zihao; Zhan, Ningxin; Zheng, Jieyi; Lou, Hongming; Zhou, Mingsong; Yang, Dongjie

2015-10-01

Effect of the molecular structure of lignin-based polyoxyethylene ether (EHL-PEG) on enzymatic hydrolysis of Avicel and corn stover was investigated. With the increase of PEG contents and molecular weight of EHL-PEG, glucose yield of corn stover increased. EHL-PEG enhanced enzymatic hydrolysis of corn stover significantly at buffer pH 4.8-5.5. Glucose yield of corn stover at 20% solid content increased from 32.8% to 63.8% by adding EHL-PEG, while that with PEG4600 was 54.2%. Effect of EHL-PEG on enzymatic hydrolysis kinetics of cellulose film was studied by quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM). An enhancing mechanism of EHL-PEG on enzymatic hydrolysis kinetics of cellulose was proposed. Cellulase aggregates dispersed by EHL-PEG excavated extensive cavities into the surface of cellulose film, making the film become more loose and exposed. After the maximum enzymatic hydrolysis rate, the film was mainly peeled off layer by layer until equilibrium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

PubMed

Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

2016-06-01

7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

The exploration of endocytic mechanisms of PLA-PEG nanoparticles prepared by coaxialtri-capillary electrospray-template removal method.

PubMed

Chen, Jiaming; Cao, Lihua; Cui, Yuecheng; Tu, Kehua; Wang, Hongjun; Wang, Li-Qun

2018-01-01

The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells. The cellular uptake of PLA-PEG nanoparticles was an energy dependent endocytosis process. Caveolae-mediated endocytosis was only one of endocytosis pathways in A549 cells for PLA-PEG nanoparticles, while clathrin mediated endocytosis was not involved in the endocytosis process. The endocytosed PLA-PEG nanoparticles enriched in the head of A549 cells and only a small amount of them was transported into lysosome after 24h incubation. These findings provided insights into the application of electrosprayed PLA-PEG nanoparticles in nano drug delivery field. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety of polyethylene glycol 3350 for the treatment of chronic constipation in children.

PubMed

Pashankar, Dinesh S; Loening-Baucke, Vera; Bishop, Warren P

2003-07-01

To assess the clinical and biochemical safety profile of long-term polyethylene glycol 3350 (PEG) therapy in children with chronic constipation and to assess pediatric patient acceptance of PEG therapy. Prospective observational study. Pediatric clinics at a referral center. Patients Eighty-three children (44 with chronic constipation, 39 with constipation and encopresis) receiving PEG therapy for more than 3 months. Clinical adverse effects related to PEG therapy and acceptance and compliance with PEG therapy. Serum electrolyte levels, osmolality, albumin levels, and liver and renal function test results were measured. At the time of evaluation, the mean duration of PEG therapy was 8.7 months, and the mean PEG dose was 0.75 g/kg daily. There were no major clinical adverse effects. All blood test results were normal, except for transient minimal alanine aminotransferase elevation unrelated to therapy in 9 patients. All children preferred PEG to previously used laxatives, and daily compliance was measured as good in 90% of children. Long-term PEG therapy is safe and is well accepted by children with chronic constipation with and without encopresis.

Lifelong Transfer Learning for Heterogeneous Teams of Agents in Sequential Decision Processes

DTIC Science & Technology

2016-06-01

making (SDM) tasks in dynamic environments with simulated and physical robots . 15. SUBJECT TERMS Sequential decision making, lifelong learning, transfer...sequential decision-making (SDM) tasks in dynamic environments with both simple benchmark tasks and more complex aerial and ground robot tasks. Our work...and ground robots in the presence of disturbances: We applied our methods to the problem of learning controllers for robots with novel disturbances in

Utilization Deficiencies and Transfer of Strategies in Preschoolers

ERIC Educational Resources Information Center

Clerc, Jerome; Miller, Patricia H.

2013-01-01

Three studies examined whether strategy utilization deficiencies emerge during transfer to two tasks that differ superficially from the main task but have the same underlying structural logic. In Experiment 1, children aged 4, 4 1/2, and 5 spontaneously produced selective attention strategies (or were prompted to do so) on a selective memory task.…

Vernier perceptual learning transfers to completely untrained retinal locations after double training: A “piggybacking” effect

PubMed Central

Wang, Rui; Zhang, Jun-Yun; Klein, Stanley A.; Levi, Dennis M.; Yu, Cong

2014-01-01

Perceptual learning, a process in which training improves visual discrimination, is often specific to the trained retinal location, and this location specificity is frequently regarded as an indication of neural plasticity in the retinotopic visual cortex. However, our previous studies have shown that “double training” enables location-specific perceptual learning, such as Vernier learning, to completely transfer to a new location where an irrelevant task is practiced. Here we show that Vernier learning can be actuated by less location-specific orientation or motion-direction learning to transfer to completely untrained retinal locations. This “piggybacking” effect occurs even if both tasks are trained at the same retinal location. However, piggybacking does not occur when the Vernier task is paired with a more location-specific contrast-discrimination task. This previously unknown complexity challenges the current understanding of perceptual learning and its specificity/transfer. Orientation and motion-direction learning, but not contrast and Vernier learning, appears to activate a global process that allows learning transfer to untrained locations. Moreover, when paired with orientation or motion-direction learning, Vernier learning may be “piggybacked” by the activated global process to transfer to other untrained retinal locations. How this task-specific global activation process is achieved is as yet unknown. PMID:25398974

MSAll strategy for comprehensive quantitative analysis of PEGylated-doxorubicin, PEG and doxorubicin by LC-high resolution q-q-TOF mass spectrometry coupled with all window acquisition of all fragment ion spectra.

PubMed

Yin, Lei; Su, Chong; Ren, Tianming; Meng, Xiangjun; Shi, Meiyun; Paul Fawcett, J; Zhang, Mengliang; Hu, Wei; Gu, Jingkai

2017-11-06

The covalent attachment of polyethylene glycol (PEG) to therapeutic compounds (known as PEGylation) is one of the most promising techniques to improve the biological efficacy of small molecular weight drugs. After administration, PEGylated prodrugs can be metabolized into pharmacologically active compounds so that PEGylated drug, free drug and released PEG are present simultaneously in the body. Understanding the pharmacokinetic behavior of these three compounds is needed to guide the development of pegylated theranostic agents. However, PEGs are polydisperse molecules with a wide range of molecular weights, so that the simultaneous quantitation of PEGs and PEGylated molecules in biological matrices is very challenging. This article reports the application of a data-independent acquisition method (MS All ) based on liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-q-q-TOF-MS) in the positive ion mode to the simultaneous determination of methoxyPEG2000-doxorubicin (mPEG2K-Dox) and its breakdown products in rat blood. Using the MS All technique, precursor ions of all molecules are generated in q1, fragmented to product ions in q2 (collision cell), and subjected to TOF separation before precursor and product ions are recorded using low and high collision energies (CE) respectively in different experiments for a single sample injection. In this study, dissociation in q2 generated a series of high resolution PEG-related product ions at m/z 89.0611, 133.0869, 177.1102, 221.1366, 265.1622, 309.1878, and 353.2108 corresponding to fragments containing various numbers of ethylene oxide subunits, Dox-related product ions at m/z 321.0838 and 361.0785, and an mPEG2K-Dox specific product ion at m/z 365.0735. Detection of mPEGs and mPEG2K-Dox was based on high resolution extracted ions of mPEG and the specific compound. The method was successfully applied to a pharmacokinetic study of doxorubicin, mPEG2K (methylated polyethylene glycol 2K), and mPEG2K-doxorubicin in rats after a single intravenous injection of mPEG2K-doxorubicin. To the best of our knowledge, this is the first assay that simultaneously determines mPEG, Dox, and mPEG2K-Dox in a biological matrix. We believe the MS All technique as applied in this study can be potentially extended to the determination of other PEGylated small molecules or polymeric compounds.

Glucose-functionalized Au nanoprisms for optoacoustic imaging and near-infrared photothermal therapy

NASA Astrophysics Data System (ADS)

Han, Jishu; Zhang, Jingjing; Yang, Meng; Cui, Daxiang; de La Fuente, Jesus M.

2015-12-01

Targeted imaging and tumor therapy using nanomaterials has stimulated research interest recently, but the high cytotoxicity and low cellular uptake of nanomaterials limit their bioapplication. In this paper, glucose (Glc) was chosen to functionalize Au nanoprisms (NPrs) for improving the cytotoxicity and cellular uptake of Au@PEG-Glc NPrs into cancer cells. Glucose is a primary source of energy at the cellular level and at cellular membranes for cell recognition. A coating of glucose facilitates the accumulation of Au@PEG-Glc NPrs in a tumor region much more than Au@PEG NPrs. Due to the high accumulation and excellent photoabsorbing property of Au@PEG-Glc NPrs, enhanced optoacoustic imaging of a tumor in vivo was achieved, and visualization of the tumor further guided cancer treatment. Based on the optical-thermal conversion performance of Au@PEG-Glc NPrs, the tumor in vivo was effectively cured through photothermal therapy. The current work demonstrates the great potential of Au@PEG-Glc NPrs in optoacoustic imaging and photothermal cancer therapy in future.Targeted imaging and tumor therapy using nanomaterials has stimulated research interest recently, but the high cytotoxicity and low cellular uptake of nanomaterials limit their bioapplication. In this paper, glucose (Glc) was chosen to functionalize Au nanoprisms (NPrs) for improving the cytotoxicity and cellular uptake of Au@PEG-Glc NPrs into cancer cells. Glucose is a primary source of energy at the cellular level and at cellular membranes for cell recognition. A coating of glucose facilitates the accumulation of Au@PEG-Glc NPrs in a tumor region much more than Au@PEG NPrs. Due to the high accumulation and excellent photoabsorbing property of Au@PEG-Glc NPrs, enhanced optoacoustic imaging of a tumor in vivo was achieved, and visualization of the tumor further guided cancer treatment. Based on the optical-thermal conversion performance of Au@PEG-Glc NPrs, the tumor in vivo was effectively cured through photothermal therapy. The current work demonstrates the great potential of Au@PEG-Glc NPrs in optoacoustic imaging and photothermal cancer therapy in future. Electronic supplementary information (ESI) available: The evolution of the UV-vis absorption of Au NPrs by centrifugation, TEM image of PEG-capped Au NPrs, the UV-vis absorption of glucose, cytotoxicity of Au@PEG-Glc NPrs, gastric cell viabilities versus the concentration of Au@PEG-Glc NPrs and gastric cell viabilities filled with 80 μg Au@PEG-Glc NPrs versus the irradiation time, optoacoustic signals of Au NPr solution and Au@PEG NPrs. See DOI: 10.1039/c5nr06261f

Does self-efficacy mediate transfer effects in the learning of easy and difficult motor skills?

PubMed

Stevens, David; Anderson, David I; O'Dwyer, Nicholas J; Mark Williams, A

2012-09-01

The effect of task difficulty on inter-task transfer is a classic issue in motor learning. We examined the relation between self-efficacy and transfer of learning after practicing different versions of a stick balancing task. Practicing the same task or an easier version led to significant pre- to post-test transfer of learning, whereas practicing a more difficult version did not. Self-efficacy increased modestly from pre- to post-test with easy practice, but decreased significantly with difficult practice. In addition, self-efficacy immediately prior to the post-test was significantly lower after difficult practice than easy or intermediate practice. Self-efficacy immediately prior to the post-test, performance at the end of practice, and pre-test performance explained 75% of the variance in post-test performance. The mediating role of self-efficacy on transfer of learning offers an alternative explanation for recent findings on the superiority of easy-to-difficult transfer and may help clarify inconsistencies in earlier research. Copyright © 2012 Elsevier Inc. All rights reserved.

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

PubMed

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Beverage intake preference and bowel preparation laxative taste preference for colonoscopy

PubMed Central

Laiyemo, Adeyinka O; Burnside, Clinton; Laiyemo, Maryam A; Kwagyan, John; Williams, Carla D; Idowu, Kolapo A; Ashktorab, Hassan; Kibreab, Angesom; Scott, Victor F; Sanderson, Andrew K

2015-01-01

AIM: To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. METHODS: We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1st, 2nd, and 3rd based on their taste preferences. Our primary outcome is the number of 1st place rankings for each preparation. RESULTS: A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1st by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. CONCLUSION: Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable. PMID:26261736

Beverage intake preference and bowel preparation laxative taste preference for colonoscopy.

PubMed

Laiyemo, Adeyinka O; Burnside, Clinton; Laiyemo, Maryam A; Kwagyan, John; Williams, Carla D; Idowu, Kolapo A; Ashktorab, Hassan; Kibreab, Angesom; Scott, Victor F; Sanderson, Andrew K

2015-08-06

To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1(st), 2(nd), and 3(rd) based on their taste preferences. Our primary outcome is the number of 1(st) place rankings for each preparation. A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1(st) by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable.

PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs.

PubMed

Turecek, Peter L; Bossard, Mary J; Schoetens, Freddy; Ivens, Inge A

2016-02-01

Modification of biopharmaceutical molecules by covalent conjugation of polyethylene glycol (PEG) molecules is known to enhance pharmacologic and pharmaceutical properties of proteins and other large molecules and has been used successfully in 12 approved drugs. Both linear and branched-chain PEG reagents with molecular sizes of up to 40 kDa have been used with a variety of different PEG derivatives with different linker chemistries. This review describes the properties of PEG itself, the history and evolution of PEGylation chemistry, and provides examples of PEGylated drugs with an established medical history. A trend toward the use of complex PEG architectures and larger PEG polymers, but with very pure and well-characterized PEG reagents is described. Nonclinical toxicology findings related to PEG in approved PEGylated biopharmaceuticals are summarized. The effect attributed to the PEG part of the molecules as observed in 5 of the 12 marketed products was cellular vacuolation seen microscopically mainly in phagocytic cells which is likely related to their biological function to absorb and remove particles and macromolecules from blood and tissues. Experience with marketed PEGylated products indicates that adverse effects in toxicology studies are usually related to the active part of the drug but not to the PEG moiety. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Recent development of poly(ethylene glycol)-cholesterol conjugates as drug delivery systems.

PubMed

He, Zhi-Yao; Chu, Bing-Yang; Wei, Xia-Wei; Li, Jiao; Edwards, Carl K; Song, Xiang-Rong; He, Gu; Xie, Yong-Mei; Wei, Yu-Quan; Qian, Zhi-Yong

2014-07-20

Poly(ethylene glycol)-cholesterol (PEG-Chol) conjugates are composed of "hydrophilically-flexible" PEG and "hydrophobically-rigid" Chol molecules. PEG-Chol conjugates are capable of forming micelles through molecular self-assembly and they are also used extensively for the PEGylation of drug delivery systems (DDS). The PEGylated DDS have been shown to display optimized physical stability properties in vitro and longer half-lives in vivo when compared with non-PEGylated DDS. Cell uptake studies have indicated that PEG-Chol conjugates are internalized via clathrin-independent pathways into endosomes and Golgi apparatus. Acid-labile PEG-Chol conjugates are also able to promote the content release of PEGylated DDS when triggered by dePEGylation at acidic conditions. More importantly, biodegradable PEG-Chol molecules have been shown to decrease the "accelerated blood clearance" phenomenon of PEG-DSPE. Ligands, peptides or antibodies which have been modified with PEG-Chols are oftentimes used to formulate active targeting DDS, which have been shown in many systems recently to enhance the efficacy and lower the adverse effects of drugs. Production of PEG-Chol is simple and efficient, and production costs are relatively low. In conclusion, PEG-Chol conjugates appear to be very promising multifunctional biomaterials for many uses in the biomedical sciences and pharmaceutical industries. Copyright © 2014 Elsevier B.V. All rights reserved.

New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

PubMed Central

Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

1998-01-01

Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

Activation of the Prefrontal Cortex While Performing a Task at Preferred Slow Pace and Metronome Slow Pace: A Functional Near-Infrared Spectroscopy Study

PubMed Central

Moriguchi, Yoshiya

2014-01-01

Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions. PMID:25436155

Developing and Evaluating In Vitro Effect of Poly(Ethylene Glycol) Conjugated Curcumin on Human Cancer Cell Lines.

PubMed

Tung, Bui Thanh; Hai, Nguyen Thanh; Son, Phan Ke

2016-01-01

Curcumin has been shown to possess strong cytotoxic effect against various cancer cell lines. However, curcumin has not applied as a drug for treatment of cancer yet due to low solubility in water and low bioavailability. The aims of this study were to prepare a new polyethylene glycol (PEG) conjugated curcumin and to evaluate its antitumor activity in vitro. PEG-CUR was prepared by the reaction between curcumin and PEG. PEG-CUR which was characterized by SEM, TEM, FTIR, DSC and 1H NMR analysis. The physicochemical parameters of PEG-CUR such as zeta potential, size distribution, solubility and percentage of curcumin were also investigated. Our results showed that the percentage of curcumin in PEG-CUR was 13.26 ± 1.25 %. PEG-CUR has nanosize values of 96.3 nm and the zeta potential values of - 48.4 mV. The PEG-CUR showed significantly increasing curcumin's solubility in water and another medium such as in 0,1 N HCl, phosphate buffer pH 4.5 and pH 6.8 solution and n-octanol. Our data also have shown cytotoxicity effect of PEG-CUR was much greater than curcumin-free in two different HepG2 and HCT116 cancer cell lines. It could be concluded from our results that the PEG-CUR may be a potential candidate for cancer treatment. Further studies are needed to evaluate the antitumor efficacy of PEG-CUR in vivo.

Successful Transfer of a Motor Learning Strategy to a Novel Sport.

PubMed

Kearney, Philip E; Judge, Phil

2017-10-01

This study investigated whether secondary school students who were taught a motor learning strategy could transfer their knowledge of the strategy to learning a novel task. Twenty adolescents were randomly allocated to a strategy or control group. The strategy group was taught Singer's five-step learning strategy, while the control group received information on the evolution and biomechanics of the basketball free throw. Both groups received three 1-hour practice sessions on a modified basketball shooting task. After one month, participants were introduced to the transfer task, golf putting. Performance accuracy was recorded for all tasks, and participants completed questionnaires regarding strategy use during practice. Participants taught the five-step learning strategy successfully recalled and applied it after a 1-month interval, and they demonstrated superior performance on both acquisition and transfer tasks, relative to the control group. Physical education teachers and coaches should consider using this learning strategy to enhance the learning of closed motor skills.

Computer-based training for improving mental calculation in third- and fifth-graders.

PubMed

Caviola, Sara; Gerotto, Giulia; Mammarella, Irene C

2016-11-01

The literature on intervention programs to improve arithmetical abilities is fragmentary and few studies have examined training on the symbolic representation of numbers (i.e. Arabic digits). In the present research, three groups of 3rd- and 5th-grade schoolchildren were given training on mental additions: 76 were assigned to a computer-based strategic training (ST) group, 73 to a process-based training (PBT) group, and 71 to a passive control (PC) group. Before and after the training, the children were given a criterion task involving complex addition problems, a nearest transfer task on complex subtraction problems, two near transfer tasks on math fluency, and a far transfer task on numerical reasoning. Our results showed developmental differences: 3rd-graders benefited more from the ST, with transfer effects on subtraction problems and math fluency, while 5th-graders benefited more from the PBT, improving their response times in the criterion task. Developmental, clinical and educational implications of these findings are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Evidence for Narrow Transfer after Short-Term Cognitive Training in Older Adults.

PubMed

Souders, Dustin J; Boot, Walter R; Blocker, Kenneth; Vitale, Thomas; Roque, Nelson A; Charness, Neil

2017-01-01

The degree to which "brain training" can improve general cognition, resulting in improved performance on tasks dissimilar from the trained tasks (transfer of training), is a controversial topic. Here, we tested the degree to which cognitive training, in the form of gamified training activities that have demonstrated some degree of success in the past, might result in broad transfer. Sixty older adults were randomly assigned to a gamified cognitive training intervention or to an active control condition that involved playing word and number puzzle games. Participants were provided with tablet computers and asked to engage in their assigned training for 30 45-min training sessions over the course of 1 month. Although intervention adherence was acceptable, little evidence for transfer was observed except for the performance of one task that most resembled the gamified cognitive training: There was a trend for greater improvement on a version of the corsi block tapping task for the cognitive training group relative to the control group. This task was very similar to one of the training games. Results suggest that participants were learning specific skills and strategies from game training that influenced their performance on a similar task. However, even this near-transfer effect was weak. Although the results were not positive with respect to broad transfer of training, longer duration studies with larger samples and the addition of a retention period are necessary before the benefit of this specific intervention can be ruled out.

Large-scale protein/antibody patterning with limiting unspecific adsorption

NASA Astrophysics Data System (ADS)

Fedorenko, Viktoriia; Bechelany, Mikhael; Janot, Jean-Marc; Smyntyna, Valentyn; Balme, Sebastien

2017-10-01

A simple synthetic route based on nanosphere lithography has been developed in order to design a large-scale nanoarray for specific control of protein anchoring. This technique based on two-dimensional (2D) colloidal crystals composed of polystyrene spheres allows the easy and inexpensive fabrication of large arrays (up to several centimeters) by reducing the cost. A silicon wafer coated with a thin adhesion layer of chromium (15 nm) and a layer of gold (50 nm) is used as a substrate. PS spheres are deposited on the gold surface using the floating-transferring technique. The PS spheres were then functionalized with PEG-biotin and the defects by self-assembly monolayer (SAM) PEG to prevent unspecific adsorption. Using epifluorescence microscopy, we show that after immersion of sample on target protein (avidin and anti-avidin) solution, the latter are specifically located on polystyrene spheres. Thus, these results are meaningful for exploration of devices based on a large-scale nanoarray of PS spheres and can be used for detection of target proteins or simply to pattern a surface with specific proteins.

Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.

PubMed

Martin, Irene; Dohmen, Christian; Mas-Moruno, Carlos; Troiber, Christina; Kos, Petra; Schaffert, David; Lächelt, Ulrich; Teixidó, Meritxell; Günther, Michael; Kessler, Horst; Giralt, Ernest; Wagner, Ernst

2012-04-28

In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and α(v)β(3) integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer. This journal is © The Royal Society of Chemistry 2012

Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery.

PubMed

Chen, Chih-Kuang; Lin, Wei-Jen; Hsia, Yu; Lo, Leu-Wei

2017-03-01

Well-defined poly(ethylene glycol)-b-allyl functional polylactide-b-polylactides (PEG-APLA-PLAs) are synthesized through sequential ring-opening polymerization. PEG-APLA-PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core-shell interface cross-linked micelles (ICMs) by micellization and UV-initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological-mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug-ICM formulations possess slow and sustained drug release profiles under physiological-mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox-loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross-linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers.

PubMed

McCarthy, M R; Vandegriff, K D; Winslow, R M

2001-08-30

We compared rates of oxygen transport in an in vitro capillary system using red blood cells (RBCs) and cell-free hemoglobins. The axial PO(2) drop down the capillary was calculated using finite-element analysis. RBCs, unmodified hemoglobin (HbA(0)), cross-linked hemoglobin (alpha alpha-Hb) and hemoglobin conjugated to polyethylene-glycol (PEG-Hb) were evaluated. According to their fractional saturation curves, PEG-Hb showed the least desaturation down the capillary, which most closely matched the RBCs; HbA(0) and alpha alpha-Hb showed much greater desaturation. A lumped diffusion parameter, K*, was calculated based on the Fick diffusion equation with a term for facilitated diffusion. The overall rates of oxygen transfer are consistent with hemoglobin diffusion rates according to the Stokes-Einstein Law and with previously measured blood pressure responses in rats. This study provides a conceptual framework for the design of a 'blood substitute' based on mimicking O(2) transport by RBCs to prevent autoregulatory changes in blood flow and pressure.

Supramolecular assembled three-dimensional graphene hybrids: Synthesis and applications in supercapacitors

NASA Astrophysics Data System (ADS)

Ni, Lubin; Zhang, Wang; Wu, Zhen; Sun, Chunyu; Cai, Yin; Yang, Guang; Chen, Ming; Piao, Yuanzhe; Diao, Guowang

2017-02-01

Graphene-based materials have received worldwide attention in the focus of forefront energy storage investigations. Currently, the design of novel three-dimensional (3D) graphene structures with high energy capability, superior electron and ion conductivity, and robust mechanical flexibility is still a great challenge. Herein, we have successfully demonstrated a novel approach to fabricate 3D assembled graphene through the supramolecular interactions of β-cyclodextrin polymers (β-CDP) with an adamantine end-capped poly(ethylene oxide) polymer linker (PEG-AD). The incorporation of PEG-AD linker into rGO sheets increased the interlayer spacing of rGO sheets to form 3D graphene materials, which can provide efficient 3D electron transfer pathways and ion diffusion channels, and facilitate the infiltration of gel electrolyte. The as-prepared 3D self-assembled graphene materials exhibit significantly improved electrochemical performances of supercapacitor in terms of high specific capacitance, remarkable rate capability, and excellent cycling stability compared to pristine reduced graphene oxide. This study shed new lights to the construction of three dimensional self-assembled graphene materials and their urgent applications in energy storage.

Incorporating functionalized polyethylene glycol lipids into reprecipitated conjugated polymer nanoparticles for bioconjugation and targeted labeling of cells

NASA Astrophysics Data System (ADS)

Kandel, Prakash K.; Fernando, Lawrence P.; Ackroyd, P. Christine; Christensen, Kenneth A.

2011-03-01

We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing.We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing. Electronic supplementary information (ESI) available: Additional TEM data, supplemental light scattering measurements, absorbance and fluorescence emission spectra, and photostability measurements. See DOI: 10.1039/c0nr00746c

Interlimb transfer of motor skill learning during walking: No evidence for asymmetric transfer.

PubMed

Krishnan, Chandramouli; Ranganathan, Rajiv; Tetarbe, Manik

2017-07-01

Several studies have shown that learning a motor skill in one limb can transfer to the opposite limb-a phenomenon called as interlimb transfer. The transfer of motor skills between limbs, however, has shown to be asymmetric, where one side benefits to a greater extent than the other. While this phenomenon has been well-documented in the upper-extremity, evidence for interlimb transfer in the lower-extremity is limited and mixed. This study investigated the extent of interlimb transfer during walking, and tested whether this transfer was asymmetric using a foot trajectory-tracking paradigm that has been specifically used for gait rehabilitation. The paradigm involved learning a new gait pattern which required greater hip and knee flexion during the swing phase of the gait while walking on a treadmill. Twenty young adults were randomized into two equal groups, where one group (right-to-left: RL) practiced the task initially with the dominant right leg and the other group (left-to-right: LR) practiced the task initially with their non-dominant left leg. After training, both groups practiced the task with their opposite leg to test the transfer effects. The changes in tracking error on each leg were computed to quantify learning and transfer effects. The results indicated that practice with one leg improved the motor performance of the other leg; however, the amount of transfer was similar across groups, indicating that there was no asymmetry in transfer. This finding is contradictory to most upper-extremity studies (where asymmetric transfer has been reported) and points out that both differences in neural processes and types of tasks may mediate interlimb transfer. Copyright © 2017 Elsevier B.V. All rights reserved.

Polyethyleneglycol/silver functionalized reduced graphene oxide aerogel for environmental application

NASA Astrophysics Data System (ADS)

Kumari, G. Vanitha; Asha, S.; Ananth, A. Nimrodh; Rajan, M. A. Jothi; Mathavan, T.

2018-04-01

Polyethylene glycol (PEG)/Silver (Ag) functionalized reduced graphene oxide aerogel (RGOA) was synthesized. PEG/Ag decorated reduced graphene oxide aerogel was characterized using XRD, Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR). The surface morphology of PEG/Ag/RGOA was analyzed using scanning electron microscope. The non-covalent interaction between reduced graphene oxide layers and the interaction between PEG and Ag on RGOA were studied by FT-IR spectra. It was observed that the interaction between Ag and PEG could enhance the properties of RGOA. Methyl Orange (MO) dye degradation was observed from UV-Vis Spectra. The process was studied by monitoring the simultaneous decrease in the height of UV-Vis absorption peak of dye solution. The results show that PEG/RGOA and PEG/Ag/RGOA are an efficient catalyst for dye degradation.

Cell separation by immunoaffinity partitioning with polyethylene glycol-modified Protein A in aqueous polymer two-phase systems

NASA Technical Reports Server (NTRS)

Karr, Laurel J.; Van Alstine, James M.; Snyder, Robert S.; Shafer, Steven G.; Harris, J. Milton

1988-01-01

Previous work has shown that polyethylene glycol (PEG)-bound antibodies can be used as affinity ligands in PEG-dextran two-phase systems to provide selective partitioning of cells to the PEG-rich phase. In the present work it is shown that immunoaffinity partitioning can be simplified by use of PEG-modified Protein A which complexes with unmodified antibody and cells and shifts their partitioning into the PEG-rich phase, thus eliminating the need to prepare a PEG-modified antibody for each cell type. In addition, the paper provides a more rigorous test of the original technique with PEG-bound antibodies by showing that it is effective at shifting the partitioning of either cell type of a mixture of two cell populations.

Can pegylated interferon improve the outcome of polycythemia vera patients?

PubMed

Crisà, Elena; Cerrano, Marco; Beggiato, Eloise; Benevolo, Giulia; Lanzarone, Giuseppe; Manzini, Paola Maria; Borchiellini, Alessandra; Riera, Ludovica; Boccadoro, Mario; Ferrero, Dario

2017-01-13

Pegylated interferon (peg-IFN) was proven by phase II trials to be effective in polycythemia vera (PV); however, it is not clear whether it could improve patient outcome compared to hydroxyurea (HU). Here, we present an observational study on 65 PV patients aged 65 years or younger, who received either peg-IFN (30) or HU (35) according to the physician choice. Median follow-up was 75 months. The two cohorts were comparable for patient and disease characteristics. Eighty-seven percent of the patients treated with peg-INF responded, with a CR rate of 70% as compared to 100 and 49% with HU, respectively. Discontinuation rate was similar in the two groups (20% in peg-IFN vs 17% in HU). JAK2 allele burden was monitored in peg-INF arm only, and a reduction was observed in 88% of the patients. No thrombotic events were observed during peg-IFN treatment compared to three on HU. Disease progression to myelofibrosis or acute myeloid leukemia occurred to a patient only in peg-INF, compared to three in HU. Overall, three second malignancies were observed during the study, two in patients who received HU only, and one in a patient largely treated HU who received also peg-IFN for 3 months. Overall survival was significantly better for peg-IFN patients compared to HU, p = 0.027. Our study, albeit limited by small patient and event number and lack of randomization, confirms the efficacy of peg-INF in PV and shows a significant survival advantage for peg-INF-treated patients. Waiting for confirming data from the ongoing phase III trials, our study can support peg-INF as a first-line treatment option for PV, at least for younger patients.

PNA-PEG modified silicon platforms as functional bio-interfaces for applications in DNA microarrays and biosensors.

PubMed

Cattani-Scholz, Anna; Pedone, Daniel; Blobner, Florian; Abstreiter, Gerhard; Schwartz, Jeffrey; Tornow, Marc; Andruzzi, Luisa

2009-03-09

The synthesis and characterization of two types of silicon-based biofunctional interfaces are reported; each interface bonds a dense layer of poly(ethylene glycol) (PEG(n)) and peptide nucleic acid (PNA) probes. Phosphonate self-assembled monolayers were derivatized with PNA using a maleimido-terminated PEG(45). Similarly, siloxane monolayers were functionalized with PNA using a maleimido-terminated PEG(45) spacer and were subsequently modified with a shorter methoxy-terminated PEG(12) ("back-filling"). The long PEG(45) spacer was used to distance the PNA probe from the surface and to minimize undesirable nonspecific adsorption of DNA analyte. The short PEG(12) "back-filler" was used to provide additional passivation of the surface against nonspecific DNA adsorption. X-ray photoelectron spectroscopic (XPS) analysis near the C 1s and N 1s ionization edges was done to characterize chemical groups formed in the near-surface region, which confirmed binding of PEG and PNA to the phosphonate and silane films. XPS also indicated that additional PEG chains were tethered to the surface during the back-filling process. Fluorescence hybridization experiments were carried out with complementary and noncDNA strands; both phosphonate and siloxane biofunctional surfaces were effective for hybridization of cDNA strands and significantly reduced nonspecific adsorption of the analyte. Spatial patterns were prepared by polydimethylsiloxane (PDMS) micromolding on the PNA-functionalized surfaces; selective hybridization of fluorescently labeled DNA was shown at the PNA functionalized regions, and physisorption at the probe-less PEG-functionalized regions was dramatically reduced. These results show that PNA-PEG derivatized phosphonate monolayers hold promise for the smooth integration of device surface chemistry with semiconductor technology for the fabrication of DNA biosensors. In addition, our results confirm that PNA-PEG derivatized self-assembled carboxyalkylsiloxane films are promising substrates for DNA microarray applications.

[Multifunctional nano-vector for gene delivery into human adipose derived mesenchymal stem cells and in vitro cellular magnetic resonance imaging].

PubMed

Pang, Pengfei; Li, Bing; Hu, Xiaojun; Kang, Zhuang; Guan, Shouhai; Gong, Faming; Meng, Xiaochun; Li, Dan; Huang, Mingsheng; Shan, Hong

2014-04-08

To examine the feasibility and efficacy of using superparamagnetic iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine (PEG-g-PEI-SPION) as a carrier for gene delivery into human adipose derived mesenchymal stem cells (hADMSCs) and in vitro cellular magnetic resonance imaging (MRI). PEG-g-PEI-SPION was synthesized as previously reported. Gel electrophoresis was performed to assess the pDNA condensation capacity of PEG-g-PEI-SPION. The particle size and zeta potential of PEG-g-PEI-SPION/pDNA complexes were determined by dynamic light scattering. Cytotoxicity of PEG-g-PEI-SPION was evaluated by CCK-8 assay with hADMSCs. Gene transfection efficiency of PEG-g-PEI-SPION in hADMSCs was quantified by flow cytometry. The cellular internalization of PEG-g-PEI-SPION/pDNA nanocomplexes was studied by confocal laser scanning microscopy and Prussian blue staining. MRI function of PEG-g-PEI-SPION was studied by in vitro cellular MRI scanning. PEG-g-PEI-SPION condensed pDNA to form stable complexes of 80-100 nm in diameter and showed low cytotoxicity in hADMSCs. At the optimal N/P ratio of 20, PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of 22.8% ± 3.6% in hADMSCs. And it was higher than that obtained with lipofectamine 11.2% ± 2.6% (P < 0.05). Furthermore, hADMSCs labeled with PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2-weighted images in vitro. PEG-g-PEI-SPION is an efficient and MRI-visible nano-vector for gene delivery into hADMSCs.

Development of a novel biocompatible poly(ethylene glycol)-block-poly(γ-cholesterol-L-glutamate) as hydrophobic drug carrier.

PubMed

Ma, Qing; Li, Bo; Yu, Yiyi; Zhang, Ying; Wu, Yang; Ren, Wen; Zheng, Yu; He, Jun; Xie, Yongmei; Song, Xiangrong; He, Gu

2013-03-10

A novel biomaterial poly(ethylene glycol)-block-poly(γ-cholesterol-l-glutamate) (mPEG-PCHLG) was designed and synthesized by introducing cholesterol side chains into this pegylated poly(amino acid) copolymers to enlarge the core space to increase the drug capacity. Paclitaxel (PTX) loaded mPEG-PCHLG nanoparticles (PTX-mPEG-PCHLG-Nps) were developed for the first time. The preparation method of nanoparticles was screened and optimized systemically. The optimal PTX-mPEG-PCHLG-Nps with the average diameter of 213.71 nm were constructed through the O/W single-emulsion solvent evaporation method. The entrapment efficiency and drug loading was 38.02 ± 4.51% and 93.90 ± 4.56%, respectively. PTX-mPEG-PCHLG-Nps were spherical and well-dispersed and displayed a dramatic sustained-release property. The in vitro cytotoxicity experiments demonstrated that the blank mPEG-PCHLG nanoparticles had no cytotoxicities on four tumor cell lines including A549, HepG-2, MCF-7 and C26, which implied that mPEG-PCHLG might be biocompatible. PTX-mPEG-PCHLG-Nps obtained the same cell growth inhibition activities as free PTX when incubated with the above tumor cells for 48h. It can be inferred that PTX-mPEG-PCHLG-Nps could probably have higher anticancer efficacy due to the inadequate release of PTX from nanoparticles. PTX-mPEG-PCHLG-Nps achieved the highest antitumor activity in A549 rather than HepG-2, MCF-7 and C26, thus PTX-mPEG-PCHLG-Nps could have a potential application in lung cancer therapy. All the data indicated that mPEG-PCHLG was one of biocompatible biomaterials and worth being widely investigated as hydrophobic antitumor drug carrier. Copyright © 2013 Elsevier B.V. All rights reserved.

Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome.

PubMed

Chapman, R W; Stanghellini, V; Geraint, M; Halphen, M

2013-09-01

Polyethylene glycol (PEG) 3350 plus electrolytes (PEG 3350+E) is an established treatment for constipation and has been proposed as a treatment option for constipation associated with irritable bowel syndrome (IBS-C). This study aimed to compare the efficacy and safety of PEG 3350+E vs. placebo in adult patients with IBS-C. Following a 14-day run-in period without study medication, patients with confirmed IBS-C were randomized to receive PEG 3350+E (N=68) or placebo (N=71) for 28 days. The primary endpoint was the mean number of spontaneous bowel movements (SBMs) per day in the last treatment week. In both groups, mean weekly number of SBMs (±s.d.) increased from run-in. The difference between the groups in week 4 (PEG 3350+E, 4.40±2.581; placebo, 3.11±1.937) was statistically significant (95% confidence interval: 1.17, 1.95; P<0.0001). Although mean severity score for abdominal discomfort/pain was significantly reduced compared with run-in with PEG 3350+E, there was no difference vs. placebo. Spontaneous complete bowel movements, responder rates, stool consistency, and severity of straining also showed superior improvement in the PEG 3350+E group over placebo in week 4. The most common drug related treatment-emergent adverse events were abdominal pain (PEG 3350+E, 4.5%; placebo, 0%) and diarrhoea (PEG 3350+E, 4.5%; placebo, 4.3%). In IBS-C, PEG 3350+E was superior to placebo for relief of constipation, and although a statistically significant improvement in abdominal discomfort/pain was observed compared with baseline, there was no associated improvement compared with placebo. PEG 3350+E is a well-established and effective treatment that should be considered suitable for use in IBS-C.

Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

PubMed

Zhao, Jing; Feng, Si-Shen

2014-03-01

Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.

A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

NASA Astrophysics Data System (ADS)

Zhang, Quan; Zhang, Xuanmiao; Chen, Tijia; Wang, Xinyi; Fu, Yao; Jin, Yun; Sun, Xun; Gong, Tao; Zhang, Zhirong

2015-05-01

A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47myr) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47myr modified PEG-Lip (preS1/21-47myr-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47myr-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47myr-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47myr-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47myr-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47myr-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47myr-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47myr-PEG-Lip in liver. Taken together, preS1/21-47myr-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.

Construction and characterization of Gal-chitosan graft methoxy poly (ethylene glycol) (Gal-CS-mPEG) nanoparticles as efficient gene carrier

NASA Astrophysics Data System (ADS)

Jin, Jiting; Fu, Wandong; Liao, Miaofei; Han, Baoqin; Chang, Jing; Yang, Yan

2017-10-01

In the present study, galactosylated chitosan (Gal-CS) was conjugated with methoxy poly(ethylene glycol) (mPEG) as a hydrophilic group. The structure of Gal-CS-mPEG polymer was characterized and the nanoparticles (NPs) were prepared using ironic gelation method. The study was designed to investigate the characteristics and functions of Gal-CS-mPEG NPs. The morphology of Gal-CS-mPEG NPs was observed by SEM and it was a compact and spherical shape. The size of the NPs was approximately 200 nm in diameter under the ideal process parameters. The interaction between Gal-CS-mPEG NPs and pDNA, and the protection of pDNA against DNase I and serum degradation by Gal-CS-mPEG NPs were evaluated. Agarose gel electrophoresis results showed that Gal-CS-mPEG NPs had strong interaction with pDNA at the weight ratio of 12:1, 4:1 and 2:1 and could protect pDNA from DNase I and serum degradation. Gal-CS-mPEG NPs exhibited high loading efficiency and sustainable in vitro release. The blood compatibility studies demonstrated that Gal-CS-mPEG NPs had superior compatibility with erythrocytes in terms of aggregation degree and hemolysis level. Gal-CS-mPEG NPs showed no cytotoxicity on L929 cells, which is a normal mouse connective tissue fibroblast, but showed inhibitory effects on the proliferation of Bel-7402 cells, which is a liver cancer cell line. In conclusion, Gal-CS-mPEG NP is a bio-safe and efficient gene carrier with potential application in gene delivery.

Solid freeform fabrication and in-vitro response of osteoblast cells of mPEG-PCL-mPEG bone scaffolds.

PubMed

Jiang, Cho-Pei; Chen, Yo-Yu; Hsieh, Ming-Fa; Lee, Hung-Maan

2013-04-01

Bone tissue engineering is an emerging approach to provide viable substitutes for bone regeneration. Poly(ethylene glycol) (PEG) is a good candidate of bone scaffold because of several advantages such as hydrophilicity, biocompatibility, and intrinsic resistance to protein adsorption and cell adhesion. However, its low compressive strength limits application for bone regeneration. Poly(ε-caprolactone) (PCL), a hydrophobic nonionic polymer, is adopted to enhance the compressive strength of PEG alone.We aimed to investigate the in-vitro response of osteoblast-like cells cultured with porous scaffolds of triblock PEG-PCL-PEG copolymer fabricated by an air pressure-aided deposition system. A desktop air pressure-aided deposition system that involves melting and plotting PEG-PCL-PEG was used to fabricate three-dimensional scaffolds having rectangular pores. The experimental results showed that PEG-PCL-PEG with a molecular weight of 25,000 can be melted and stably deposited through a heating nozzle at an air pressure of 0.3 MPa and no crack occurs after it solidifies. The scaffolds with pre-determined pore size of 400× 420 μm and a porosity of 79 % were fabricated, and their average compressive strength was found to be 18.2 MPa. Osteoblast-like cells, MC3T3-E1, were seeded on fabricated scaffolds to investigate the in-vitro response of cells including toxicity and cellular locomotion. In a culture period of 28 days, the neutral-red stained osteoblasts were found to well distributed in the interior of the scaffold. Furthermore, the cellular attachment and movement in the first 10 h of cell culture were observed with time-lapse microscopy indicating that the porous PEG-PCL-PEG scaffolds fabricated by air pressure-aided deposition system is non-toxicity for osteoblast-like cells.

Interaction of poly(ethylene-glycols) with air-water interfaces and lipid monolayers: investigations on surface pressure and surface potential.

PubMed Central

Winterhalter, M; Bürner, H; Marzinka, S; Benz, R; Kasianowicz, J J

1995-01-01

We have characterized the surface activity of different-sized poly(ethylene-glycols) (PEG; M(r) 200-100,000 Da) in the presence or absence of lipid monolayers and over a wide range of bulk PEG concentrations (10(-8)-10% w/v). Measurements of the surface potential and surface pressure demonstrate that PEGs interact with the air-water and lipid-water interfaces. Without lipid, PEG added either to the subphase or to the air-water interface forms relatively stable monolayers. Except for very low molecular weight polymers (PEGs < 1000 Da), low concentrations of PEG in the subphase (between 10(-5) and 10(-4)% w/v) increase the surface potential from zero (with respect to the potential of a pure air-water interface) to a plateau value of approximately 440 mV. At much higher polymer concentrations, > 10(-1)% (w/v), depending on the molecular weight of the PEG and corresponding to the concentration at which the polymers in solution are likely to overlap, the surface potential decreases. High concentrations of PEG in the subphase cause a similar decrease in the surface potential of densely packed lipid monolayers spread from either diphytanoyl phosphatidylcholine (DPhPC), dipalmitoyl phosphatidylcholine (DPPC), or dioleoyl phosphatidylserine (DOPS). Adding PEG as a monolayer at the air-water interface also affects the surface activity of DPhPC or DPPC monolayers. At low lipid concentration, the surface pressure and potential are determined by the polymer. For intermediate lipid concentrations, the surface pressure-area and surface potential-area isotherms show that the effects due to lipid and PEG are not always additive and that the polymer's effect is distinct for the two lipids. When PEG-lipid-mixed monolayers are compressed to surface pressures greater than the collapse pressure for a PEG monolayer, the surface pressure-area and surface potential-area isotherms approach that of the lipid alone, suggesting that for this experimental condition PEG is expelled from the interface. PMID:8534807

The effects of a two-step transfer on a visuomotor adaptation task.

PubMed

Aiken, Christopher A; Pan, Zhujun; Van Gemmert, Arend W A

2017-11-01

The literature has shown robust effects of transfer-of-learning to the contralateral side and more recently transfer-of-learning effects to a new effector type on the ipsilateral side. Few studies have investigated the effects of transfer-of-learning when skills transfer to both a new effector type and the contralateral side (two-step transfer). The purpose of the current study was to investigate the effects of two-step transfer and to examine which aspects of the movement transfer and which aspects do not. Individuals practiced a 30° visual rotation task with either the dominant or non-dominant limb and with either the use of the fingers and wrist or elbow and shoulder. Following practice, participants performed the task with the untrained effector type on the contralateral side. Results showed that initial direction error and trajectory length transferred from the dominant to the non-dominant side and movement time transferred from the elbow and shoulder condition to the wrist and finger conditions irrespective of which limb was used during practice. The results offer a unique perspective on the current theoretical and practical implications for transfer-of-learning and are further discussed in this paper.

Pharmacokinetic analysis of multi PEG-theophylline conjugates.

PubMed

Grassi, Mario; Bonora, Gian Maria; Drioli, Sara; Cateni, Francesca; Zacchigna, Marina

2012-10-01

In the attempt of prolonging the effect of drugs, a new branched, high-molecular weight multimeric poly(ethylene glycol) (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as drug carrier. In particular, the attention was focused on the study of theophylline (THEO) and THEO-MultiPEG conjugates pharmacokinetic after oral administration in rabbit. Pharmacokinetic behavior was studied according to an ad hoc developed mathematical model accounting for THEO-MultiPEG in vivo absorption and decomposition into drug (THEO) and carrier (MultiPEG). The branched high-molecular weight MultiPEG proved to be a reliable drug delivery system able to prolong theophylline staying in the blood after oral administration of a THEO-MultiPEG solution. The analysis of experimental data by means of the developed mathematical model revealed that the prolongation of THEO effect was essentially due to the low THEO-MultiPEG permeability in comparison to that of pure THEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Separation and quantitation of polyethylene glycols 400 and 3350 from human urine by high-performance liquid chromatography.

PubMed

Ryan, C M; Yarmush, M L; Tompkins, R G

1992-04-01

Polyethylene glycol 3350 (PEG 3350) is useful as an orally administered probe to measure in vivo intestinal permeability to macromolecules. Previous methods to detect polyethylene glycol (PEG) excreted in the urine have been hampered by inherent inaccuracies associated with liquid-liquid extraction and turbidimetric analysis. For accurate quantitation by previous methods, radioactive labels were required. This paper describes a method to separate and quantitate PEG 3350 and PEG 400 in human urine that is independent of radioactive labels and is accurate in clinical practice. The method uses sized regenerated cellulose membranes and mixed ion-exchange resin for sample preparation and high-performance liquid chromatography with refractive index detection for analysis. The 24-h excretion for normal individuals after an oral dose of 40 g of PEG 3350 and 5 g of PEG 400 was 0.12 +/- 0.04% of the original dose of PEG 3350 and 26.3 +/- 5.1% of the original dose of PEG 400.

Effects of Strategy Instruction on the Learning, Use, and Vertical Transfer of Strategies.

ERIC Educational Resources Information Center

Finley, Fred N.; Smith, Edward L.

1980-01-01

Compares group differences in strategy learning, use, and transfer to a more complex task for two groups of elementary students (N=48). Asked to perform three tasks in classifying igneous rocks, the groups differed in whether they received advice on the use of a specific strategy for performing each task. (CS)

Alleviation of Osmotic Stress Effects by Exogenous Application of Salicylic or Abscisic Acid on Wheat Seedlings

PubMed Central

Marcińska, Izabela; Czyczyło-Mysza, Ilona; Skrzypek, Edyta; Grzesiak, Maciej T.; Janowiak, Franciszek; Filek, Maria; Dziurka, Michał; Dziurka, Kinga; Waligórski, Piotr; Juzoń, Katarzyna; Cyganek, Katarzyna; Grzesiak, Stanisław

2013-01-01

The aim of the study was to assess the role of salicylic acid (SA) and abscisic acid (ABA) in osmotic stress tolerance of wheat seedlings. This was accomplished by determining the impact of the acids applied exogenously on seedlings grown under osmotic stress in hydroponics. The investigation was unique in its comprehensiveness, examining changes under osmotic stress and other conditions, and testing a number of parameters simultaneously. In both drought susceptible (SQ1) and drought resistant (CS) wheat cultivars, significant physiological and biochemical changes were observed upon the addition of SA (0.05 mM) or ABA (0.1 μM) to solutions containing half-strength Hoagland medium and PEG 6000 (−0.75 MPa). The most noticeable result of supplementing SA or ABA to the medium (PEG + SA and PEG + ABA) was a decrease in the length of leaves and roots in both cultivars. While PEG treatment reduced gas exchange parameters, chlorophyll content in CS, and osmotic potential, and conversely, increased lipid peroxidation, soluble carbohydrates in SQ1, proline content in both cultivars and total antioxidants activity in SQ1, PEG + SA or PEG + ABA did not change the values of these parameters. Furthermore, PEG caused a two-fold increase of endogenous ABA content in SQ1 and a four-fold increase in CS. PEG + ABA increased endogenous ABA only in SQ1, whereas PEG + SA caused a greater increase of ABA content in both cultivars compared to PEG. In PEG-treated plants growing until the harvest, a greater decrease of yield components was observed in SQ1 than in CS. PEG + SA, and particularly PEG + ABA, caused a greater increase of these yield parameters in CS compared to SQ1. In conclusion, SA and ABA ameliorate, particularly in the tolerant wheat cultivar, the harmful effects and after effects of osmotic stress induced by PEG in hydroponics through better osmotic adjustment achieved by an increase in proline and carbohydrate content as well as by an increase in antioxidant activity. PMID:23803653

Comparison between different colon cleansing products for screening colonoscopy. A noninferiority trial in population-based screening programs in Italy.

PubMed

Zorzi, Manuel; Valiante, Flavio; Germanà, Bastianello; Baldassarre, Gianluca; Coria, Bartolomea; Rinaldi, Michela; Heras Salvat, Helena; Carta, Alessandra; Bortoluzzi, Francesco; Cervellin, Erica; Polo, Maria Luisa; Bulighin, Gianmarco; Azzurro, Maurizio; Di Piramo, Daniele; Turrin, Anna; Monica, Fabio

2016-03-01

The high volume and poor palatability of 4 L of polyethylene glycol (PEG)-based bowel cleansing preparation required before a colonoscopy represent a major obstacle for patients. The aim of this study was to compare two low volume PEG-based preparations with standard 4 L PEG in individuals with a positive fecal immunochemical test (FIT) within organized screening programs in Italy. A total of 3660 patients with a positive FIT result were randomized to receive, in a split-dose regimen, 4 L PEG or 2 L PEG plus ascorbate (PEG-A) or 2 L PEG with citrate and simethicone plus bisacodyl (PEG-CS). The noninferiority of the low volume preparations vs. 4 L PEG was tested through the difference in proportions of adequate cleansing. A total of 2802 patients were included in the study. Adequate bowel cleansing was achieved in 868 of 926 cases (93.7 %) in the 4 L PEG group, in 872 out of 911 cases in the PEG-A group (95.7 %, difference in proportions  + 1.9 %, 95 % confidence interval [CI]  - 0.1 to 3.9), and in 862 out of 921 cases in the PEG-CS group (93.6 %, difference in proportions  - 0.2 %, 95 %CI  - 2.4 to 2.0). Bowel cleansing was adequate in 95.5 % of cases when the preparation-to-colonoscopy interval was between 120 and 239 minutes, whereas it dropped to 83.3 % with longer intervals. Better cleansing was observed in patients with regular bowel movements (95.6 %) compared with those with diarrhea (92.4 %) or constipation (90.8 %). Low volume PEG-based preparations administered in a split-dose regimen guarantee noninferior bowel cleansing compared with 4 L PEG. Constipated patients require a personalized preparation. EudraCT 2012 - 003958 - 82. © Georg Thieme Verlag KG Stuttgart · New York.

Inhibition mechanism of P-glycoprotein mediated efflux by mPEG-PLA and influence of PLA chain length on P-glycoprotein inhibition activity.

PubMed

Li, Wenjing; Li, Xinru; Gao, Yajie; Zhou, Yanxia; Ma, Shujin; Zhao, Yong; Li, Jinwen; Liu, Yan; Wang, Xinglin; Yin, Dongdong

2014-01-06

The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

Neural correlates of training and transfer effects in working memory in older adults.

PubMed

Heinzel, Stephan; Lorenz, Robert C; Pelz, Patricia; Heinz, Andreas; Walter, Henrik; Kathmann, Norbert; Rapp, Michael A; Stelzel, Christine

2016-07-01

As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12sessions (45min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Thrive or overload? The effect of task complexity on novices' simulation-based learning.

PubMed

Haji, Faizal A; Cheung, Jeffrey J H; Woods, Nicole; Regehr, Glenn; de Ribaupierre, Sandrine; Dubrowski, Adam

2016-09-01

Fidelity is widely viewed as an important element of simulation instructional design based on its purported relationship with transfer of learning. However, higher levels of fidelity may increase task complexity to a point at which novices' cognitive resources become overloaded. In this experiment, we investigate the effects of variations in task complexity on novices' cognitive load and learning during simulation-based procedural skills training. Thirty-eight medical students were randomly assigned to simulation training on a simple or complex lumbar puncture (LP) task. Participants completed four practice trials on this task (skill acquisition). After 10 days of rest, all participants completed one additional trial on their assigned task (retention) and one trial on a 'very complex' simulation designed to be similar to the complex task (transfer). We assessed LP performance and cognitive load on each trial using multiple measures. In both groups, LP performance improved significantly during skill acquisition (p ≤ 0.047, f = 0.29-0.96) and was maintained at retention. The simple task group demonstrated superior performance compared with the complex task group throughout these phases (p ≤ 0.002, d = 1.13-2.31). Cognitive load declined significantly in the simple task group (p < 0.009, f = 0.48-0.76), but not in the complex task group during skill acquisition, and remained lower at retention (p ≤ 0.024, d = 0.78-1.39). Between retention and transfer, LP performance declined and cognitive load increased in the simple task group, whereas both remained stable in the complex task group. At transfer, no group differences were observed in LP performance and cognitive load, except that the simple task group made significantly fewer breaches of sterility (p = 0.023, d = 0.80). Reduced task complexity was associated with superior LP performance and lower cognitive load during skill acquisition and retention, but mixed results on transfer to a more complex task. These results indicate that task complexity is an important factor that may mediate (via cognitive overload) the relationship between instructional design elements (e.g. fidelity) and simulation-based learning outcomes. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Effective Bayesian Transfer Learning

DTIC Science & Technology

2010-03-01

reasonable value of k , defined by the task B training set size. Transfer Regret 1 Regret = 100 * G AB B No Transfer With Transfer AB...a. REPORT U b . ABSTRACT U c. THIS PAGE U 19b. TELEPHONE NUMBER (Include area code) N/A Standard Form 298 (Rev. 8-98) Prescribed...rule set given the prior and developed staged approximate inference strategy, in which data from observed tasks 1 to k are used to infer general rule

Enhancing perceptual and attentional skills requires common demands between the action video games and transfer tasks.

PubMed

Oei, Adam C; Patterson, Michael D

2015-01-01

Despite increasing evidence that shows action video game play improves perceptual and cognitive skills, the mechanisms of transfer are not well-understood. In line with previous work, we suggest that transfer is dependent upon common demands between the game and transfer task. In the current study, participants played one of four action games with varying speed, visual, and attentional demands for 20 h. We examined whether training enhanced performance for attentional blink, selective attention, attending to multiple items, visual search and auditory detection. Non-gamers who played the game (Modern Combat) with the highest demands showed transfer to tasks of attentional blink and attending to multiple items. The game (MGS Touch) with fewer attentional demands also decreased attentional blink, but to a lesser degree. Other games failed to show transfer, despite having many action game characteristics but at a reduced intensity. The results support the common demands hypothesis.

Enhancing perceptual and attentional skills requires common demands between the action video games and transfer tasks

PubMed Central

Oei, Adam C.; Patterson, Michael D.

2015-01-01

Despite increasing evidence that shows action video game play improves perceptual and cognitive skills, the mechanisms of transfer are not well-understood. In line with previous work, we suggest that transfer is dependent upon common demands between the game and transfer task. In the current study, participants played one of four action games with varying speed, visual, and attentional demands for 20 h. We examined whether training enhanced performance for attentional blink, selective attention, attending to multiple items, visual search and auditory detection. Non-gamers who played the game (Modern Combat) with the highest demands showed transfer to tasks of attentional blink and attending to multiple items. The game (MGS Touch) with fewer attentional demands also decreased attentional blink, but to a lesser degree. Other games failed to show transfer, despite having many action game characteristics but at a reduced intensity. The results support the common demands hypothesis. PMID:25713551

An Experimental Investigation of Potential Icing of the Space Shuttle External Tank,

DTIC Science & Technology

1982-09-01

PEG 4000, a PEG 1000/400 mixture, and PEG 6000. The number corresponds to the molecular weight of the compound. 2 4.65m Foam Inslation Side 8 ob o 4m(l...Level Emiseivity panel (PEG coated) (Uncoated) Emissivity Panel Left Right 1 4.4 -28.8 -31.6 4.7 -12.2 -15.3 2 4.4 -20.2 -22.2 4.7 -12.8 -13.4 3 4.3...constant dry bulb temperature of 60*F. PEG was tested on one half of side A of the panel. A mixture of 450 g of molecular weight 4000 PEG and 400 g of H20

Effects of PEG4000 template on sol-gel synthesis of porous cerium titanate photocatalyst

NASA Astrophysics Data System (ADS)

Zhang, Wenjie; Tao, Yingjie; Li, Chuanguo

2018-04-01

Porous cerium titanate was synthesized by sol-gel method, using polyethylene glycol (PEG4000) as template agent. Brannerite structured CeTi2O6 in monoclinic system is the major substance formed in the materials. Formation of CeO2 and rutile TiO2 depends on the amount of PEG4000. The addition of PEG4000 leads to production of fine particles in the samples, but it does not apparently affect the band gap energy. Pore volume of the cerium titanate sample continuously increases with rising PEG4000 amount. The sample obtained using 3.5 g PEG4000 has BET surface area of 16.2 m2/g and pore volume of 0.0232 cm3/g. The addition of PEG4000 can obviously promote photocatalytic activity of cerium titanate, which can be proven by both enhanced production of hydroxyl radical and ofloxacin degradation efficiency. As much as 95.2% of the initial ofloxacin molecules are removed from the solution after 50 min of photocatalytic degradation on the cerium titanate obtained using 3.5 g PEG4000, while only 48.4% ofloxacin is removed on cerium titanate obtained without PEG4000.

Effect of polyethylene glycol on the liquid–liquid phase transition in aqueous protein solutions

PubMed Central

Annunziata, Onofrio; Asherie, Neer; Lomakin, Aleksey; Pande, Jayanti; Ogun, Olutayo; Benedek, George B.

2002-01-01

We have studied the effect of polyethylene glycol (PEG) on the liquid–liquid phase separation (LLPS) of aqueous solutions of bovine γD-crystallin (γD), a protein in the eye lens. We observe that the phase separation temperature increases with both PEG concentration and PEG molecular weight. PEG partitioning, which is the difference between the PEG concentration in the two coexisting phases, has been measured experimentally and observed to increase with PEG molecular weight. The measurements of both LLPS temperature and PEG partitioning in the ternary γD-PEG-water systems are used to successfully predict the location of the liquid–liquid phase boundary of the binary γD-water system. We show that our LLPS measurements can be also used to estimate the protein solubility as a function of the concentration of crystallizing agents. Moreover, the slope of the tie-lines and the dependence of LLPS temperature on polymer concentration provide a powerful and sensitive check of the validity of excluded volume models. Finally, we show that the increase of the LLPS temperature with PEG concentration is due to attractive protein–protein interactions. PMID:12391331

Working memory updating and binding training: Bayesian evidence supporting the absence of transfer.

PubMed

De Simoni, Carla; von Bastian, Claudia C

2018-06-01

As working memory (WM) predicts a wide range of other abilities, it has become a popular target for training interventions. However, its effectiveness to elicit generalized cognitive benefits is still under debate. Previous research yielded inconsistent findings and focused only little on the mechanisms underlying transfer effects. To disentangle training effects on WM capacity and efficiency, we evaluated near transfer to untrained, structurally different WM tasks and far transfer to closely related abilities (i.e., reasoning, processing speed, task switching, and inhibitory control) in addition to process-specific effects on 3 WM mechanisms (i.e., focus switching, removal of WM contents, and interference resolution). We randomly assigned 197 young adults to 1 of 2 experimental groups (updating or item-to-context binding) or to an active control group practicing visual search tasks. Before and after 5 weeks of adaptive training, performance was assessed measuring each of the cognitive processes and abilities of interest with 4 tasks covering verbal-numerical and visual-spatial materials. Despite the relatively large sample size, large practice effects in the trained tasks, and at least moderate correlations between WM training tasks and transfer measures, we found consistent evidence for the absence of any training-induced improvements across all ranges of transfer and mechanisms. Instead, additional analyses of error patterns and self-reported strategy use indicated that WM training encouraged the development of stimulus-specific expertise and use of paradigm-specific strategies. Thus, the results suggest that the WM training interventions examined here enhanced neither WM capacity nor the WM mechanisms assumed to underlie transfer. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Electrospinning synthesis and characterization of PLA-PEG-MNPs composite fibrous membranes

NASA Astrophysics Data System (ADS)

Kumar, M.; Klimke, S.; Preiss, A.; Unruh, D.; Wengerowsky, D.; Lehmann, R.; Sindelar, R.; Klingelhöfer, G.; Boča, R.; Renz, F.

2017-11-01

An electrospinning technique was used to fabricate PLA, PLA-PEG and PLA-PEG-MNPs composite fibrous membranes. The morphology of electrospun composite membranes were characterized by scanning electron microscope. To test the potential availability of MNPs in PLA-PEG composite membranes, TG, Raman, Mössbauer, VSM and ICP-OES analysis were used. The PLA-PEG composite fibrous membranes showed the presence of MNPs, hence offers the possibility for magnetically triggered on-demand drug delivery.

Cellular delivery of PEGylated PLGA nanoparticles.

PubMed

Pamujula, Sarala; Hazari, Sidhartha; Bolden, Gevoni; Graves, Richard A; Chinta, Dakshinamurthy Devanga; Dash, Srikanta; Kishore, Vimal; Mandal, Tarun K

2012-01-01

The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer cells. Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 µm filter to obtain target size particles (114-335 nm) with zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di-block (10% PEG) nanoparticles. These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties.

PubMed

Avgoustakis, K; Beletsi, A; Panagi, Z; Klepetsanis, P; Karydas, A G; Ithakissios, D S

2002-02-19

The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB/c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and/or targeting of cisplatin.

A method to optimize PEG-coating of red blood cells.

PubMed

Hashemi-Najafabadi, Sameereh; Vasheghani-Farahani, Ebrahim; Shojaosadati, Seyed Abbas; Rasaee, Mohammad Javad; Armstrong, Jonathan K; Moin, Mostafa; Pourpak, Zahra

2006-01-01

Alloimmunization to donor blood group antigens remains a significant problem in transfusion medicine. A proposed method to overcome donor-recipient blood group incompatibility is to mask the blood group antigens by the covalent attachment of poly(ethylene glycol) (PEG) to the red blood cell (RBC) membrane. Despite much work in the development of PEG-coating of RBCs, there is a paucity of data on the optimization of the PEG-coating technique; it is the aim of this study to determine the optimum conditions for PEG coating using a cyanuric chloride reactive derivative of methoxy-PEG as a model polymer. Activated PEG of molecular mass 5 kDa was covalently attached to human RBCs under various reaction conditions. Inhibition of binding of a blood-type specific antiserum (anti-D) was employed to evaluate the effect of the PEG-coating, quantified by hemocytometry and flow-cytometry. RBC morphology was examined by light and scanning electron microscopy. Statistical analysis of experimental design together with microscopy results showed that the optimum PEGylation conditions are pH = 8.7, temperature = 14 degrees C, and reaction time = 30 min. An optimum concentration of reactive PEG could not be determined. At high polymer concentrations (>25 mg/mL) a predominance of type III echinocytes was observed, and as a result, a concentration of 15 mg/mL is the highest recommended concentration for a linear PEG of molecular mass 5 kDa.

Exploring inter-task transfer following a CO-OP approach with four children with DCD: A single subject multiple baseline design.

PubMed

Capistran, Julie; Martini, Rose

2016-10-01

Cognitive Orientation to daily Occupational Performance (CO-OP) approach has been shown to be effective for improving the performance of tasks worked on in therapy and the use of cognitive strategies. No study to date seems to have explored its effectiveness for improving performance of untrained tasks (inter-task transfer) in children with Developmental Coordination Disorder (DCD). This study aimed to determine whether CO-OP leads to improved performance in an untrained task. A single-subject design with multiple baselines across skills was adopted, with three replications. Four children with DCD (7-12years) received 10 sessions of CO-OP intervention where each child worked on three tasks during therapy sessions and a fourth task was identified, but not worked on, to verify inter-task transfer. Task performance was rated over four phases (baseline, intervention, post-intervention, follow-up) using the Performance Quality Rating Scale (PQRS-OD). Graphed data was statistically analyzed using a two or three standard deviation band method. Significant improvement was obtained for 11 of 12 tasks worked on during therapy and for two of the four untrained tasks. These results indicate that the effectiveness of CO-OP to improve untrained tasks in children merit further exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study.

PubMed

Azin, Mahdieh; Zangiabadi, Nasser; Iranmanesh, Farhad; Baneshi, Mohammad Reza; Banihashem, Seyedshahab

2016-10-01

Intermittent theta burst stimulation (iTBS) is a repetitive transcranial magnetic stimulation (rTMS) protocol that influences cortical excitability and motor function recovery. This study aimed to investigate the effects of iTBS on manual dexterity and hand motor imagery in multiple sclerosis (MS) patients. Thirty-six MS patients were non-randomly assigned into sham (control) or iTBS groups. Then, iTBS was delivered to the primary motor cortex for ten days over two consecutive weeks. The patients' manual dexterity was assessed using the nine-hole peg test (9HPT) and the Box and Block Test (BBT), while the hand motor imagery was assessed with the hand mental rotation task (HMRT). iTBS group showed a reduction in the time required to complete the 9HPT (mean difference = -3.05, P = 0.002), and an increase in the number of blocks transferred in one minute in the BBT (mean difference = 8.9, P = 0.001) when compared to the control group. Furthermore, there was no significant difference between the two groups in terms of the reaction time (P = 0.761) and response accuracy rate (P = 0.482) in the HMRT. When iTBS was applied over the primary motor cortex, it significantly improved manual dexterity, but had no significant effect on the hand motor imagery ability in MS patients.

EVA: laparoscopic instrument tracking based on Endoscopic Video Analysis for psychomotor skills assessment.

PubMed

Oropesa, Ignacio; Sánchez-González, Patricia; Chmarra, Magdalena K; Lamata, Pablo; Fernández, Alvaro; Sánchez-Margallo, Juan A; Jansen, Frank Willem; Dankelman, Jenny; Sánchez-Margallo, Francisco M; Gómez, Enrique J

2013-03-01

The EVA (Endoscopic Video Analysis) tracking system is a new system for extracting motions of laparoscopic instruments based on nonobtrusive video tracking. The feasibility of using EVA in laparoscopic settings has been tested in a box trainer setup. EVA makes use of an algorithm that employs information of the laparoscopic instrument's shaft edges in the image, the instrument's insertion point, and the camera's optical center to track the three-dimensional position of the instrument tip. A validation study of EVA comprised a comparison of the measurements achieved with EVA and the TrEndo tracking system. To this end, 42 participants (16 novices, 22 residents, and 4 experts) were asked to perform a peg transfer task in a box trainer. Ten motion-based metrics were used to assess their performance. Construct validation of the EVA has been obtained for seven motion-based metrics. Concurrent validation revealed that there is a strong correlation between the results obtained by EVA and the TrEndo for metrics, such as path length (ρ = 0.97), average speed (ρ = 0.94), or economy of volume (ρ = 0.85), proving the viability of EVA. EVA has been successfully validated in a box trainer setup, showing the potential of endoscopic video analysis to assess laparoscopic psychomotor skills. The results encourage further implementation of video tracking in training setups and image-guided surgery.

A retention index system for comprehensive two-dimensional gas chromatography using polyethylene glycols.

PubMed

Veenaas, Cathrin; Haglund, Peter

2018-02-09

The characterization and identification of compounds in complex real-world samples is quite difficult and new concepts and workflows are highly desirable. Retention indices (RIs) are widely used in gas chromatography (GC) to support the identification of unknown compounds. Several attempts have been made to introduce a similar concept for the second dimension in comprehensive two-dimensional (2D) GC (GC × GC) but, an easily applicable and robust system remains elusive. In the present study, a new RI system for GC × GC was developed. Polyethylene glycols (PEGs) were used in combination with a simple linear regression, with n-alkanes as reference points for virtually unretained compounds and PEG homologs as reference compounds for second-dimension RIs (PEG- 2 I). The n-alkanes were assigned a PEG- 2 I of zero and the distance between consecutive PEG homologs from PEG-2 (diethylene glycol) and higher were assigned a PEG- 2 I value of 10. We used ethylene glycol and PEG-2 through PEG-10 as reference compounds, thereby covering a PEG- 2 I range from 20.0 for ethylene glycol, over 50.0 for diethylene glycol (PEG-2) to 130.0 for decaethylene glycol (PEG-10); additional PEGs can be added to cover a wider polarity range. The PEG- 2 I system was initially evaluated using a 30 m × 0.25 mm non-polar (5% phenyl, 0.25 μm film thickness) first-dimension column and a 1.6 m × 0.18 mm polar (50% phenyl, 0.18 μm film thickness) second-dimension column. This system was validated for use with non-polar first-dimension columns and a semi-polar (50% phenyl) second-dimension column, and exhibited robustness to changes in the carrier gas flow velocity, oven temperature ramping rate, and secondary oven temperature offset. An average relative standard deviation of 2.7%, equal to a 95% confidence interval of 1.27 PEG- 2 I units, was obtained for the PEG- 2 I values of 72 environmental pollutants. Additionally, the system was found to be applicable over a wide range of boiling points (in the current case, from n-heptane to n-dotriacontane (C 7 -C 32 )) and can be used with various column dimensions. Changing the second-dimension column to either a narrower 0.1 mm column or a wider 0.25 mm column, yielded similar 95%-percentiles to that of the 0.18 mm column, differing by only 3.20 and 2.80 PEG- 2 I units, respectively. Moreover, methods for improving the system were suggested. Copyright © 2017 Elsevier B.V. All rights reserved.

Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

PubMed

Sahiner, Umit M; Yavuz, S Tolga; Gökce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

2013-08-01

In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

Site-Specific Albumination as an Alternative to PEGylation for the Enhanced Serum Half-Life in Vivo.

PubMed

Yang, Byungseop; Lim, Sung In; Kim, Jong Chul; Tae, Giyoong; Kwon, Inchan

2016-05-09

Polyethylene glycol (PEG) has been widely used as a serum half-life extender of therapeutic proteins. However, due to immune responses and low degradability of PEG, developing serum half-life extender alternatives to PEG is required. Human serum albumin (HSA) has several beneficial features as a serum half-life extender, including a very long serum half-life, good degradability, and low immune responses. In order to further evaluate the efficacy of HSA, we compared the extent of serum half-life extension of a target protein, superfolder green fluorescent protein (sfGFP), upon HSA conjugation with PEG conjugation side-by-side. Combination of site-specific incorporation of p-azido-l-phenylalanine into sfGFP and copper-free click chemistry achieved the site-specific conjugation of a single HSA, 20 kDa PEG, or 30 kDa PEG to sfGFP. These sfGFP conjugates exhibited the fluorescence comparable to or even greater than that of wild-type sfGFP (sfGFP-WT). In mice, HSA-conjugation to sfGFP extended the serum half-life 9.0 times compared to that of unmodified sfGFP, which is comparable to those of PEG-conjugated sfGFPs (7.3 times for 20 kDa PEG and 9.5 times for 30 kDa PEG). These results clearly demonstrated that HSA was as effective as PEG in extending the serum half-life of a target protein. Therefore, with the additional favorable features, HSA is a good serum half-life extender of a (therapeutic) protein as an alternative to PEG.

Adenovirus vector covalently conjugated to polyethylene glycol with a cancer-specific promoter suppresses the tumor growth through systemic administration.

PubMed

Yao, Xinglei; Yoshioka, Yasuo; Morishige, Tomohiro; Eto, Yusuke; Narimatsu, Shogo; Mizuguchi, Hiroyuki; Mukai, Yohei; Okada, Naoki; Nakagawa, Shinsaku

2010-01-01

Cancer gene therapy with adenovirus vectors (Adv) is limited to local administration because systemic administration of Adv produces a weak therapeutic effect and severe side effects. Previously, we generated a dual cancer-specific Adv system by using Adv covalently conjugated to polyethylene glycol (PEG) for transductional targeting and the telomere reverse transcriptase (TERT) promoter as a cancer-specific promoter for transcriptional targeting (PEG-Ad-TERT). We demonstrated that systemic administration of PEG-Ad-TERT showed superior antitumor effects against lung metastatic cancer with negligible side effects. Here, we investigated the therapeutic efficacy of systemic administration of PEG-Ad-TERT for the treatment of primary tumors. We first evaluated the transgene expression of PEG-Ad-TERT containing the luciferase gene (PEG-Ad-TERT/Luc) in primary tumors. Systemic administration of PEG-Ad-TERT/Luc resulted high transgene expression, similar to that observed in tumors for the conventional cytomegalovirus (CMV) promoter-driven Adv containing the luciferase gene (Ad-CMV/Luc). By comparison, transgene expression was 2500-fold lower than that of Ad-CMV/Luc in liver. We then examined the therapeutic effect of systemic administration of PEG-Ad-TERT containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk) for the treatment of primary tumors. We showed that PEG-Ad-TERT/HSVtk produced a notable antitumor effect against primary tumors with negligible side effects. These results demonstrated that PEG-Ad-TERT can be regarded as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both metastatic and primary tumors.

Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

PubMed

Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

2016-03-15

Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization, efficacy, pharmacokinetics, and biodistribution of 5kDa mPEG modified tetrameric canine uricase variant.

PubMed

Zhang, Chun; Fan, Kai; Luo, Hua; Ma, Xuefeng; Liu, Riyong; Yang, Li; Hu, Chunlan; Chen, Zhenmin; Min, Zhiqiang; Wei, Dongzhi

2012-07-01

PEGylated uricase is a promising anti-gout drug, but the only commercially marketed 10kDa mPEG modified porcine-like uricase (Pegloticase) can only be used for intravenous infusion. In this study, tetrameric canine uricase variant was modified by covalent conjugation of all accessible ɛ amino sites of lysine residues with a smaller 5kDa mPEG (mPEG-UHC). The average modification degree and PEGylation homogeneity were evaluated. Approximately 9.4 5 kDa mPEG chains were coupled to each monomeric uricase and the main conjugates contained 7-11 mPEG chains per subunit. mPEG-UHC showed significantly therapeutic or preventive effect on uric acid nephropathy and acute urate arthritis based on three different animal models. The clearance rate from an intravenous injection of mPEG-UHC varied significantly between species, at 2.61 mL/h/kg for rats and 0.21 mL/h/kg for monkeys. The long elimination half-life of mPEG-UHC in non-human primate (191.48 h, intravenous injection) indicated the long-term effects in humans. Moreover, the acceptable bioavailability of mPEG-UHC after subcutaneous administration in monkeys (94.21%) suggested that subcutaneous injection may be regarded as a candidate administration route in clinical trails. Non-specific tissue distribution was observed after administration of (125)I-labeled mPEG-UHC in rats, and elimination by the kidneys into the urine is the primary excretion route. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice

PubMed Central

Zhang, Guodong; Yang, Zhi; Lu, Wei; Zhang, Rui; Huang, Qian; Tian, Mei; Li, Li; Liang, Dong; Li, Chun

2009-01-01

Polyethylene glycol (PEG)-coated (pegylated) gold nanoparticles (AuNPs) have been proposed as drug carriers and diagnostic contrast agents. However, the impact of particle characteristics on the biodistribution and pharmacokinetics of pegylated AuNPs is not clear. We investigated the effects of PEG molecular weight, type of anchoring ligand, and particle size on the assembly properties and colloidal stability of PEG-coated AuNPs. The pharmacokinetics and biodistribution of the most stable PEG-coated AuNPs in nude mice bearing subcutaneous A431 squamous tumors were further studied using 111In-labeled AuNPs. AuNPs coated with thioctic acid (TA)-anchored PEG exhibited higher colloidal stability in phosphate-buffered saline in the presence of dithiothreitol than did AuNPs coated with monothiol-anchored PEG. AuNPs coated with high-molecular-weight (5000 Da) PEG were more stable than AuNPs coated with low-molecular-weight (2000 Da) PEG. Of the 20-nm, 40-nm, and 80-nm AuNPs coated with TA-terminated PEG5000, the 20-nm AuNPs exhibited the lowest uptake by reticuloendothelial cells and the slowest clearance from the body. Moreover, the 20-nm AuNPs coated with TA-terminated PEG5000 showed significantly higher tumor uptake and extravasation from the tumor blood vessels than did the 40- and 80-nm AuNPs. Thus, 20-nm AuNPs coated with TA-terminated PEG5000 are promising potential drug delivery vehicles and diagnostic imaging agents. PMID:19131103

Investigation of the role of hydrophilic chain length in amphiphilic perfluoropolyether/poly(ethylene glycol) networks: towards high-performance antifouling coatings.

PubMed

Wang, Yapei; Pitet, Louis M; Finlay, John A; Brewer, Lenora H; Cone, Gemma; Betts, Douglas E; Callow, Maureen E; Callow, James A; Wendt, Dean E; Hillmyer, Marc A; DeSimonea, Joseph M

2011-01-01

The facile preparation of amphiphilic network coatings having a hydrophobic dimethacryloxy-functionalized perfluoropolyether (PFPE-DMA; M(w) = 1500 g mol(-1)) crosslinked with hydrophilic monomethacryloxy functionalized poly(ethylene glycol) macromonomers (PEG-MA; M(w) = 300, 475, 1100 g mol(-1)), intended as non-toxic high-performance marine coatings exhibiting antifouling characteristics is demonstrated. The PFPE-DMA was found to be miscible with the PEG-MA. Photo-cured blends of these materials containing 10 wt% of PEG-MA oligomers did not swell significantly in water. PFPE-DMA crosslinked with the highest molecular weight PEG oligomer (ie PEG1100) deterred settlement (attachment) of algal cells and cypris larvae of barnacles compared to a PFPE control coating. Dynamic mechanical analysis of these networks revealed a flexible material. Preferential segregation of the PEG segments at the polymer/air interface resulted in enhanced antifouling performance. The cured amphiphilic PFPE/PEG films showed decreased advancing and receding contact angles with increasing PEG chain length. In particular, the PFPE/PEG1100 network had a much lower advancing contact angle than static contact angle, suggesting that the PEG1100 segments diffuse to the polymer/water interface quickly. The preferential interfacial aggregation of the larger PEG segments enables the coating surface to have a substantially enhanced resistance to settlement of spores of the green seaweed Ulva, cells of the diatom Navicula and cypris larvae of the barnacle Balanus amphitrite as well as low adhesion of sporelings (young plants) of Ulva, adhesion being lower than to a polydimethyl elastomer, Silastic T2.

Time course influences transfer of visual perceptual learning across spatial location.

PubMed

Larcombe, S J; Kennard, C; Bridge, H

2017-06-01

Visual perceptual learning describes the improvement of visual perception with repeated practice. Previous research has established that the learning effects of perceptual training may be transferable to untrained stimulus attributes such as spatial location under certain circumstances. However, the mechanisms involved in transfer have not yet been fully elucidated. Here, we investigated the effect of altering training time course on the transferability of learning effects. Participants were trained on a motion direction discrimination task or a sinusoidal grating orientation discrimination task in a single visual hemifield. The 4000 training trials were either condensed into one day, or spread evenly across five training days. When participants were trained over a five-day period, there was transfer of learning to both the untrained visual hemifield and the untrained task. In contrast, when the same amount of training was condensed into a single day, participants did not show any transfer of learning. Thus, learning time course may influence the transferability of perceptual learning effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transfer of an induced preferred retinal locus of fixation to everyday life visual tasks.

PubMed

Barraza-Bernal, Maria J; Rifai, Katharina; Wahl, Siegfried

2017-12-01

Subjects develop a preferred retinal locus of fixation (PRL) under simulation of central scotoma. If systematic relocations are applied to the stimulus position, PRLs manifest at a location in favor of the stimulus relocation. The present study investigates whether the induced PRL is transferred to important visual tasks in daily life, namely pursuit eye movements, signage reading, and text reading. Fifteen subjects with normal sight participated in the study. To develop a PRL, all subjects underwent a scotoma simulation in a prior study, where five subjects were trained to develop the PRL in the left hemifield, five different subjects on the right hemifield, and the remaining five subjects could naturally chose the PRL location. The position of this PRL was used as baseline. Under central scotoma simulation, subjects performed a pursuit task, a signage reading task, and a reading-text task. In addition, retention of the behavior was also studied. Results showed that the PRL position was transferred to the pursuit task and that the vertical location of the PRL was maintained on the text reading task. However, when reading signage, a function-driven change in PRL location was observed. In addition, retention of the PRL position was observed over weeks and months. These results indicate that PRL positions can be induced and may further transferred to everyday life visual tasks, without hindering function-driven changes in PRL position.

Genetic Modulation of Training and Transfer in Older Adults: BDNF Val66Met Polymorphism is Associated with Wider Useful Field of View

PubMed Central

Colzato, Lorenza S.; van Muijden, Jesse; Band, Guido P. H.; Hommel, Bernhard

2011-01-01

Western society has an increasing proportion of older adults. Increasing age is associated with a general decrease in the control over task-relevant mental processes. In the present study we investigated the possibility that successful transfer of game-based cognitive improvements to untrained tasks in elderly people is modulated by preexisting neuro-developmental factors as genetic variability related to levels of the brain-derived neurotrophic factor (BDNF), an important neuromodulator underlying cognitive processes. We trained participants, genotyped for the BDNF Val66Met polymorphism, on cognitive tasks developed to improve dynamic attention. Pre-training (baseline) and post-training measures of attentional processes (divided and selective attention) were acquired by means of the useful field of view task. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects. PMID:21909331

Training, Retention, and Transfer of Data Entry Perceptual and Motoric Processes Over Long Retention Intervals

NASA Technical Reports Server (NTRS)

Kole, James A.; Schneider, Vivian I.; Healy, Alice F.; Barshi, Immanuel

2017-01-01

Subjects trained in a standard data entry task, which involved typing numbers (e.g., 5421) using their right hands. At test (6 months post-training), subjects completed the standard task, followed by a left-hand variant (typing with their left hands) that involved the same perceptual, but different motoric, processes as the standard task. At a second test (8 months post-training), subjects completed the standard task, followed by a code variant (translating letters into digits, then typing the digits with their right hands) that involved different perceptual, but the same motoric, processes as the standard task. For each of the three tasks, half the trials were trained numbers (old) and half were new. Repetition priming (faster response times to old than new numbers) was found for each task. Repetition priming for the standard task reflects retention of trained numbers; for the left-hand variant reflects transfer of perceptual processes; and for the code variant reflects transfer of motoric processes. There was thus evidence for both specificity and generalizability of training data entry perceptual and motoric processes over very long retention intervals.

Degree of Handedness Affects Intermanual Transfer of Skill Learning

PubMed Central

Chase, Cori; Seidler, Rachael

2008-01-01

Intermanual transfer of skill learning has often been used as a paradigm to study functional specialization and hemispheric interactions in relation to handedness. This literature has not evaluated whether degree of handedness impacts learning and intermanual transfer. Because handedness scores are related to factors that might influence intermanual transfer, such as engagement of the ipsilateral hemisphere during movement and corpus callosum volume, we tested whether degree of handedness is correlated with transfer magnitude. We had groups of left and right handed participants perform a sensorimotor adaptation task and a sequence learning task. Following learning with either the dominant or nondominant hand, participants transferred to task performance with the other hand. We evaluated whether the magnitude of learning and intermanual transfer were influenced by either direction and / or degree of handedness. Participants exhibited faster sensorimotor adaptation with the right hand, regardless of whether they were right or left handed. In addition, less strongly left handed individuals exhibited better intermanual transfer of sensorimotor adaptation, while less strongly right handed individuals exhibited better intermanual transfer of sequence learning. The findings suggest that involvement of the ipsilateral hemisphere during learning may influence intermanual transfer magnitude. PMID:18592225

Spatial parameters at the basis of social transfer of learning.

PubMed

Lugli, Luisa; Iani, Cristina; Milanese, Nadia; Sebanz, Natalie; Rubichi, Sandro

2015-06-01

Recent research indicates that practicing on a joint spatial compatibility task with an incompatible stimulus-response mapping affects subsequent joint Simon task performance, eliminating the social Simon effect. It has been well established that in individual contexts, for transfer of learning to occur, participants need to practice an incompatible association between stimulus and response positions. The mechanisms underlying transfer of learning in joint task performance are, however, less well understood. The present study was aimed at assessing the relative contribution of 3 different spatial relations characterizing the joint practice context: stimulus-response, stimulus-participant, and participant-response relations. In 3 experiments, the authors manipulated the stimulus-response, stimulus-participant, and response-participant associations. We found that learning from the practice task did not transfer to the subsequent task when during practice stimulus-response associations were spatially incompatible and stimulus-participant associations were compatible (Experiment 1). However, a transfer of learning was evident when stimulus-participant associations were spatially incompatible. This occurred both when response-participant associations were incompatible (Experiment 2) and when they were compatible (Experiment 3). These results seem to support an agent corepresentation account of correspondence effects emerging in joint settings since they suggest that, in social contexts, critical to obtain transfer-of-learning effects is the spatial relation between stimulus and participant positions while the spatial relation between stimulus and response positions is irrelevant. (c) 2015 APA, all rights reserved).

Transfer from Audiovisual Pretraining to a Continuous Perceptual Motor Task. Final Report for Period June 1972 - August 1973.

ERIC Educational Resources Information Center

Wood, Milton E.; Gerlach, Vernon S.

A technique was developed for providing transfer-of-training from a form of audiovisual pretraining to an instrument flight task. The continuous flight task was broken into discrete categories of flight; each category combined an instrument configuration with a return-to-criterion aircraft control response. Three methods of sequencing categories…

Understanding the Mind or Predicting Signal-Dependent Action? Performance of Children with and without Autism on Analogues of the False-Belief Task

ERIC Educational Resources Information Center

Bowler, Dermot M.; Briskman, Jackie; Gurvidi, Nicole; Fornells-Ambrojo, Miriam

2005-01-01

To evaluate the claim that correct performance on unexpected transfer false-belief tasks specifically involves mental-state understanding, two experiments were carried out with children with autism, intellectual disabilities, and typical development. In both experiments, children were given a standard unexpected transfer false-belief task and a…

Brain-Behavior Mechanisms for the Transfer of Neuromuscular Training Adaptions to Simulated Sport: Initial Findings from the Train the Brain Project.

PubMed

Grooms, Dustin R; Kiefer, Adam W; Riley, Michael A; Ellis, Jonathan D; Thomas, Staci; Kitchen, Katie; DiCesare, Christopher; Bonnette, Scott; Gadd, Brooke; Barber Foss, Kim D; Yuan, Weihong; Silva, Paula; Galloway, Ryan; Diekfuss, Jed; Leach, James; Berz, Kate; Myer, Gregory D

2018-03-27

A limiting factor for reducing anterior cruciate ligament (ACL) injury risk is ensuring that the movement adaptions made during the prevention program transfer to sport-specific activity. Virtual reality provides a mechanism to assess transferability and neuroimaging provides a means to assay the neural processes allowing for such skill transfer. To determine the neural mechanisms for injury risk reducing biomechanics transfer to sport after ACL injury prevention training. Cohort study Setting: Research laboratory Participants: Four healthy high school soccer athletes. Participants completed augmented neuromuscular training utilizing real-time visual feedback. An unloaded knee extension task and a loaded leg-press task was completed with neuroimaging before and after training. A virtual reality soccer specific landing task was also competed following training to assess transfer of movement mechanics. Landing mechanics during the virtual reality soccer task and blood oxygen level dependent signal change during neuroimaging. Increased motor planning, sensory and visual region activity during unloaded knee extension and decreased motor cortex activity during loaded leg-press were highly correlated with improvements in landing mechanics (decreased hip adduction and knee rotation). Changes in brain activity may underlie adaptation and transfer of injury risk reducing movement mechanics to sport activity. Clinicians may be able to target these specific brain processes with adjunctive therapy to facilitate intervention improvements transferring to sport.

The effects of ethnicity, musicianship, and tone language experience on pitch perception.

PubMed

Zheng, Yi; Samuel, Arthur G

2018-02-01

Language and music are intertwined: music training can facilitate language abilities, and language experiences can also help with some music tasks. Possible language-music transfer effects are explored in two experiments in this study. In Experiment 1, we tested native Mandarin, Korean, and English speakers on a pitch discrimination task with two types of sounds: speech sounds and fundamental frequency (F0) patterns derived from speech sounds. To control for factors that might influence participants' performance, we included cognitive ability tasks testing memory and intelligence. In addition, two music skill tasks were used to examine general transfer effects from language to music. Prior studies showing that tone language speakers have an advantage on pitch tasks have been taken as support for three alternative hypotheses: specific transfer effects, general transfer effects, and an ethnicity effect. In Experiment 1, musicians outperformed non-musicians on both speech and F0 sounds, suggesting a music-to-language transfer effect. Korean and Mandarin speakers performed similarly, and they both outperformed English speakers, providing some evidence for an ethnicity effect. Alternatively, this could be due to population selection bias. In Experiment 2, we recruited Chinese Americans approximating the native English speakers' language background to further test the ethnicity effect. Chinese Americans, regardless of their tone language experiences, performed similarly to their non-Asian American counterparts in all tasks. Therefore, although this study provides additional evidence of transfer effects across music and language, it casts doubt on the contribution of ethnicity to differences observed in pitch perception and general music abilities.

Adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals to improve its dispersity.

PubMed

Cheng, Dong; Wen, Yangbing; Wang, Lijuan; An, Xingye; Zhu, Xuhai; Ni, Yonghao

2015-06-05

In this work, the adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals (CNC) was investigated for preparing re-dispersible dried CNC. Results showed that the re-dispersity of CNC in water can be significantly enhanced using a PEG1000 dosage of 5wt% (based on the dry weight of CNC). The elemental analysis confirmed the adsorption of PEG onto the CNC surface. Transmission electron microscopy (TEM) was used to characterize the dry powder and indicated that the irreversible agglomeration of CNC after drying was essentially eliminated based on the PEG adsorption concept. Thermo-gravimetric analysis (TGA) and X-ray diffraction (XRD) suggested that CNC crystallinity and thermal stability were not affected by the adsorption of PEG. Thus, the adsorption of PEG has great potential for producing re-dispersible powder CNC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

PubMed

Lee, Hwankyu; Larson, Ronald G

2009-10-08

We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

Preventing Protein Adsorption and Macrophage Uptake of Gold Nanoparticles via a Hydrophobic Shield

PubMed Central

Larson, Timothy A.; Joshi, Pratixa P.; Sokolov, Konstantin

2012-01-01

Polyethylene glycol (PEG) surface coatings are widely used to render stealth properties to nanoparticles in biological applications. There is abundant literature on benefits of PEG coatings and their ability to reduce protein adsorption, to diminish non-specific interactions with cells, and to improve pharmacokinetics, but very little discussion of the limitations of PEG coatings. Here, we show that physiological concentrations of cysteine and cystine can displace methoxy-PEG-thiol molecules from the gold nanoparticle (GNP) surface that leads to protein adsorption and cell uptake in macrophages within 24 hours. Furthermore, we address this problem by incorporating an alkyl linker between the PEG and the thiol moieties that provides a hydrophobic shield layer between the gold surface and the hydrophilic outer PEG layer. The mPEG-alkyl-thiol coating greatly reduces protein adsorption on GNPs and their macrophage uptake. This has important implications for the design of GNP for biological systems. PMID:23009596

Achievement of Virtual and Real Objects Using a Short-Term Motor Learning Protocol in People with Duchenne Muscular Dystrophy: A Crossover Randomized Controlled Trial.

PubMed

Massetti, Thais; Fávero, Francis Meire; Menezes, Lilian Del Ciello de; Alvarez, Mayra Priscila Boscolo; Crocetta, Tânia Brusque; Guarnieri, Regiani; Nunes, Fátima L S; Monteiro, Carlos Bandeira de Mello; Silva, Talita Dias da

2018-04-01

To evaluate whether people with Duchenne muscular dystrophy (DMD) practicing a task in a virtual environment could improve performance given a similar task in a real environment, as well as distinguishing whether there is transference between performing the practice in virtual environment and then a real environment and vice versa. Twenty-two people with DMD were evaluated and divided into two groups. The goal was to reach out and touch a red cube. Group A began with the real task and had to touch a real object, and Group B began with the virtual task and had to reach a virtual object using the Kinect system. ANOVA showed that all participants decreased the movement time from the first (M = 973 ms) to the last block of acquisition (M = 783 ms) in both virtual and real tasks and motor learning could be inferred by the short-term retention and transfer task (with increasing distance of the target). However, the evaluation of task performance demonstrated that the virtual task provided an inferior performance when compared to the real task in all phases of the study, and there was no effect for sequence. Both virtual and real tasks promoted improvement of performance in the acquisition phase, short-term retention, and transfer. However, there was no transference of learning between environments. In conclusion, it is recommended that the use of virtual environments for individuals with DMD needs to be considered carefully.

Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

PubMed

Cai, Huawei; Xie, Fang; Mulgaonkar, Aditi; Chen, Lihong; Sun, Xiankai; Hsieh, Jer-Tsong; Peng, Fangyu; Tian, Rong; Li, Lin; Wu, Changqiang; Ai, Hua

2018-05-22

To synthesize and evaluate the imaging potential of Bom-PEG-[ 64 Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. [ 64 Cu]CuS NPs were synthesized in aqueous solution by 64 CuCl 2 and Na 2 S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [ 64 Cu]CuS NPs to produce Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[ 64 Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Radiolabeled Bom-PEG-[ 64 Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

Development and Validation of a New Near-Infrared Sensor to Measure Polyethylene Glycol (PEG) Concentration in Water.

PubMed

Buzzi, Olivier; Yuan, Shengyang; Routley, Benjamin

2017-06-10

A near-infrared absorption based laser sensor has been designed and validated for the real-time measurement of polyethylene glycol (PEG) concentration. The wavelength was selected after the determination of the absorption spectrum of deionised water and PEG solutions using a Varian Cary 6000i spectrophotometer, in order to limit the influence of PEG molecular mass on the absorption measurement. With this new sensor, the water is treated as the attenuating species and the addition of PEG in water reduces the absorbance of the medium. The concept was validated using three different PEG types (PEG 6,000, 20,000, and 35,000) and it was found that the results follow Beer Lambert's law. The influence of temperature was assessed by testing the PEG 20,000 at four different temperatures that could be encountered in a laboratory environment. The data show a slight temperature influence (increase of absorbance by 8% when the temperature rises from about 20 to about 29 degrees). Following the validation phase conducted ex situ, a prototype of an immersible sensor was built and calibrated for in situ measurements.

X-ray studies of recombinant anti-testosterone Fab fragments: the use of PEG 3350 in crystallization.

PubMed

Valjakka, J; Hemminki, A; Teerinen, T; Takkinen, K; Rouvinen, J

2000-02-01

Recombinant anti-testosterone wild-type Fab fragment and mutant Fab fragments with high binding selectivity developed by protein engineering have been crystallized with and without ligands. Crystals of these Fab fragments were obtained by the vapour-diffusion technique at room temperature using solutions of PEG 3350 with various biological buffers and with a wide pH range. So far, five data sets have been collected from crystals of three Fab-antigen complexes and from two uncomplexed Fab fragments, with resolutions ranging from 2.10 to 3.1 A. Crystallization conditions for Fab fragments were found by using modifications of the low ionic strength PEG 3350 series. Suitable concentrations of PEG 400, MPD and glycerol solutions for use as cryoprotectants in PEG 3350 solutions have been determined. One useful observation was that PEG 3350 is able to work alone as a cryoprotectant. The screening protocol used requires a smaller amount of protein material to achieve auspicious pre-crystals than previously. Results support the claim that PEG 3350 is more suitable for the crystallization of Fab fragments than higher molecular weight PEGs.

Validation of polyethylene glycol 3350 as a poorly absorbable marker for intestinal perfusion studies.

PubMed

Schiller, L R; Santa Ana, C A; Porter, J; Fordtran, J S

1997-01-01

Polyethylene glycol (PEG) has been used as a poorly absorbable marker in intestinal perfusion studies, but there is controversy about the absorbability of PEG, particularly when glucose-sodium cotransport is occurring. Total intestinal perfusion studies were done in five normal humans using three solutions containing 1 g/liter PEG 3350 and designed to produce low rates of water absorption, high rates of water absorption, or high rates of glucose-sodium cotransport. Water absorption rates were calculated by traditional nonabsorbable marker equations and by a novel balance technique in which absorption was taken as the difference between the volumes of solution infused and recovered during steady-state conditions. Effluent PEG recovery was 99 +/- 4%, 109 +/- 2%, and 104 +/- 6% of the amount infused with each solution. Water absorption rates measured by use of PEG concentrations were similar to those calculated by the balance technique (r = 0.99). The complete recovery of PEG confirms the poor absorbability of PEG 3350, and the excellent agreement between techniques validates PEG as a poorly absorbed marker, even when glucose-sodium cotransport is occurring.

Transferring control demands across incidental learning tasks – stronger sequence usage in serial reaction task after shortcut option in letter string checking

PubMed Central

Gaschler, Robert; Marewski, Julian N.; Wenke, Dorit; Frensch, Peter A.

2014-01-01

After incidentally learning about a hidden regularity, participants can either continue to solve the task as instructed or, alternatively, apply a shortcut. Past research suggests that the amount of conflict implied by adopting a shortcut seems to bias the decision for vs. against continuing instruction-coherent task processing. We explored whether this decision might transfer from one incidental learning task to the next. Theories that conceptualize strategy change in incidental learning as a learning-plus-decision phenomenon suggest that high demands to adhere to instruction-coherent task processing in Task 1 will impede shortcut usage in Task 2, whereas low control demands will foster it. We sequentially applied two established incidental learning tasks differing in stimuli, responses and hidden regularity (the alphabet verification task followed by the serial reaction task, SRT). While some participants experienced a complete redundancy in the task material of the alphabet verification task (low demands to adhere to instructions), for others the redundancy was only partial. Thus, shortcut application would have led to errors (high demands to follow instructions). The low control demand condition showed the strongest usage of the fixed and repeating sequence of responses in the SRT. The transfer results are in line with the learning-plus-decision view of strategy change in incidental learning, rather than with resource theories of self-control. PMID:25506336

An analysis of prognostic factors after percutaneous endoscopic gastrostomy placement in Japanese patients with amyotrophic lateral sclerosis.

PubMed

Nagashima, Kazuaki; Furuta, Natsumi; Makioka, Kouki; Fujita, Yukio; Ikeda, Masaki; Ikeda, Yoshio

2017-05-15

A percutaneous endoscopic gastrostomy (PEG) is an useful intervention for feeding of amyotrophic lateral sclerosis (ALS) patients who have lost oral intake function. The aim of this study was to investigate the risk factors for early death and the survival after PEG placement. A total of 102 ALS patients who underwent PEG placement were enrolled in this study. Patients were divided into two groups; the poor prognosis group included patients who died or needed permanent mechanical ventilation within 30days after PEG placement, and the good prognosis group included patients who did not meet the criteria of the poor prognosis group. Clinical characteristics, respiratory function, and nutritional parameters were compared for the two groups to assess the correlations between clinical and laboratory variables and early death after PEG placement. Multivariate analysis between two groups revealed that higher arterial carbon dioxide pressure (PaCO 2 ) and aphagia before PEG placement were significantly associated with the poor prognosis group. Multivariate analysis for survival also revealed that higher PaCO 2 and shorter duration from onset to PEG placement were significantly associated with shorter survival after PEG placement. In conclusion, respiratory and nutritional parameters are revealed to be important prognostic factors for ALS patients who undergo PEG placement. Copyright © 2017 Elsevier B.V. All rights reserved.

Higher Molecular Weight Polyethylene Glycol Increases Cell Proliferation While Improving Barrier Function in an In Vitro Colon Cancer Model

PubMed Central

Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C.

2011-01-01

Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor. PMID:21976966

Higher molecular weight polyethylene glycol increases cell proliferation while improving barrier function in an in vitro colon cancer model.

PubMed

Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C

2011-01-01

Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor.

The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

PubMed

Hodgman, Michael; Holland, Michael G; Englich, Ulrich; Wojcik, Susan M; Grant, William D; Leitner, Erich

2016-12-01

Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

Urinary excretion of polyethylene glycol 3350 during colonoscopy preparation.

PubMed

Rothfuss, K S; Bode, J C; Stange, E F; Parlesak, A

2006-02-01

Whole gut lavage with a polyethylene glycol electrolyte solution (PEG) is a common bowel cleansing method for diagnostic and therapeutic colon interventions. Absorption of orally administered PEG from the gastrointestinal tract in healthy human beings is generally considered to be poor. In patients with inflammatory bowel disease (IBD), intestinal permeability and PEG absorption were previously reported to be higher than in normal subjects. In the current study, we investigated the absorption of PEG 3350 in patients undergoing routine gut lavage. Urine specimens were collected for 8 hours in 24 patients undergoing bowel cleansing with PEG 3350 for colonoscopy. The urinary excretion of PEG 3350, measured by size exclusion chromatography, ranged between 0.01 and 0.51 % of the ingested amount, corresponding to 5.8 and 896 mg in absolute amounts, respectively. Mean PEG excretion in patients with impaired mucosa such as inflammation or ulceration of the intestine (0.24 % +/- 0.19, n = 11) was not significantly higher (p = 0.173) compared to that in subjects with macroscopically normal intestinal mucosa (0.13 % +/- 0.13, n = 13). The results indicate that intestinal absorption of PEG 3350 is higher than previously assumed and underlies a strong inter-individual variation. Inflammatory changes of the intestine do not necessarily lead to a significantly higher permeability of PEG.

Polyethylene glycol binding alters human telomere G-quadruplex structure by conformational selection

PubMed Central

Buscaglia, Robert; Miller, M. Clarke; Dean, William L.; Gray, Robert D.; Lane, Andrew N.; Trent, John O.; Chaires, Jonathan B.

2013-01-01

Polyethylene glycols (PEGs) are widely used to perturb the conformations of nucleic acids, including G-quadruplexes. The mechanism by which PEG alters G-quadruplex conformation is poorly understood. We describe here studies designed to determine how PEG and other co-solutes affect the conformation of the human telomeric quadruplex. Osmotic stress studies using acetonitrile and ethylene glycol show that conversion of the ‘hybrid’ conformation to an all-parallel ‘propeller’ conformation is accompanied by the release of about 17 water molecules per quadruplex and is energetically unfavorable in pure aqueous solutions. Sedimentation velocity experiments show that the propeller form is hydrodynamically larger than hybrid forms, ruling out a crowding mechanism for the conversion by PEG. PEGs do not alter water activity sufficiently to perturb quadruplex hydration by osmotic stress. PEG titration experiments are most consistent with a conformational selection mechanism in which PEG binds more strongly to the propeller conformation, and binding is coupled to the conformational transition between forms. Molecular dynamics simulations show that PEG binding to the propeller form is sterically feasible and energetically favorable. We conclude that PEG does not act by crowding and is a poor mimic of the intranuclear environment, keeping open the question of the physiologically relevant quadruplex conformation. PMID:23804761

Percutaneous Endoscopic Gastrostomy Tube Is a Negative Prognostic Factor for Recurrent/Metastatic Head and Neck Cancer.

PubMed

Siano, Marco; Jarisch, Nadine; Joerger, Markus; Espeli, Vittoria

2018-06-01

Recurrent/metastatic head and neck squamous cell cancer (r/mHNSCC) patients often need a percutaneous endoscopic gastrostomy feeding tube (PEG). Among known prognostic factors, PEG could be prognostic as well. We retrospectively analyzed r/mHNSCC patients referred for systemic treatment. Kaplan-Meier and multivariate cox regression models were applied to assess prognostic impact of PEG. One hunderd and ten patients were identified, 42 had a PEG at treatment start. Median survival from start of 1st-line systemic treatment was 8 months (95%CI=6.5-12.0 months), 4.5 months (95%CI=2.5-7.0 months) for patients with PEG and 11.5 months (95%CI=7.5-14.5 months) without PEG (adjusted HR=1.98, p=0.011). Similarly, survival from first recurrence of distant metastases was lower in patients with PEG as compared to patients without (7.5 vs. 15.5 months, adjusted HR=2.60, p<0.001). Presence of PEG feeding tube has an unfavourable prognostic impact on survival in patients with r/mHNSCC. While any causality remains speculative, potential complications should be appreciated before PEG implantation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Combined low-volume polyethylene glycol solution plus stimulant laxatives versus standard-volume polyethylene glycol solution: A prospective, randomized study of colon cleansing before colonoscopy

PubMed Central

Hookey, Lawrence C; Depew, William T; Vanner, Stephen J

2006-01-01

INTRODUCTION The effectiveness of polyethylene glycol solutions (PEG) for colon cleansing is often limited by the inability of patients to drink adequate portions of the 4 L solution. The aim of the present study was to determine whether a reduced volume of PEG combined with stimulant laxatives would be better tolerated and as or more effective than the standard dose. METHODS Patients undergoing outpatient colonoscopy were randomly assigned to receive either low-volume PEG plus sennosides (120 mg oral sennosides syrup followed by 2 L PEG) or the standard volume preparation (4 L PEG). The subjects rated the tolerability of the preparations and their symptoms. Colonoscopists were blind to the colonic cleansing preparation and graded the cleansing efficacy using a validated tool (the Ottawa scale). RESULTS The low-volume PEG plus sennosides preparation was significantly better tolerated than the standard large volume PEG (P<0.001) but was less efficacious (P=0.03). Thirty-eight per cent of patients in the large volume PEG group were unable to finish the preparation, compared with only 6% in the reduced volume group. There were no adverse events reported. CONCLUSIONS Although the low-volume PEG plus sennosides preparation was better tolerated, it was not as effective as standard large-volume PEG. However, in view of the significant difference in tolerance, further research investigating possible improvements in the reduced-volume regimen seems warranted. PMID:16482236

Nano Sponges for Drug Delivery and Medicinal Applications

NASA Technical Reports Server (NTRS)

Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dimitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jodie L., Jr.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.;