Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update.

Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.

A Comparison of Eye Movement Measures across Reading Efficiency Quartile Groups in Elementary, Middle, and High School Students in the U.S.

This cross-sectional study examined eye movements during reading across grades in stu-dents with differing levels of reading efficiency. Eye-movement recordings were obtained while students in grades 2, 4, 6, 8, 10, and 12 silently read normed grade-leveled texts with demonstrated comprehension. Recordings from students in each reading rate quartile at each grade level were compared to characterize differences in reading rate, number of fixations, number of regressions, and fixation durations. Comparisons indicated that stu-dents in higher reading rate quartiles made fewer fixations and regressions per word, and had shorter fixation durations. These indices of greater efficiency were also characteristic of students in upper as compared to lower grades, with two exceptions: (a) between grades 6 and 8, fixations and regressions increased while reading rates stagnated and fixation durations continued to decline, and (b) beyond grade 6 there was relatively little growth in the reading efficiency of students in the lower two reading rate quartiles. These results suggest that declines in fixation duration across grades may in part reflect broader matura-tional processes, while higher fixation and regression rates may distinguish students who continue to struggle with word recognition during their high school years.

The Goalposts Have Moved: Can Surgery Residents Meet Updated Quality Benchmarks for Adenoma Detection Rate in Colonoscopy?

The American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology Task Force (ACGTF) on Quality in Endoscopy released updated quality benchmarks for colonoscopy in 2015. Our initial study concluded that surgery residents could perform safe and competent screening colonoscopy within a structured endoscopy curriculum. In this follow-up study, we sought to determine whether surgery residents could achieve the increased adenoma detection rate (ADR) benchmarks endorsed by the ASGE/ACGTF. An Institutional Review Board-approved prospective analysis of colonoscopies performed by five postgraduate year 2 and 3 general surgery residents from 2013 to 2015 was completed. All colonoscopies were performed under the direct supervision of surgical endoscopists after each resident passed a structured endoscopy simulation curriculum. The following ASGE/ACG quality metrics were recorded: bowel preparation quality; cecal intubation rate; polyp and ADRs; and, complications. Power analysis determined that 108 procedures were required for an 80 per cent probability of data analysis accuracy. About 135 screening and diagnostic colonoscopies were performed. Bowel prep was considered "adequate" in 90 per cent of cases. The cecum was reached independently in 95 per cent of cases. Polyp(s) were visualized and removed in 39 per cent of patients. The overall ADR was 31.8 per cent (>25%). Male ADR was 38.7 per cent (>30%). Female ADR was 26.0 per cent (>20%). Average polyp size was 8.7 mm (range: 1-22 mm). One patient was readmitted for postpolypectomy syndrome, and successfully managed nonoperatively. In conclusion, using our structured endoscopy curriculum, surgery residents achieved ADRs fully consistent with the updated benchmark values endorsed by the ASGE/ACGTF.

Changes in Carboxy Methylation and Tyrosine Phosphorylation of Protein Phosphatase PP2A Are Associated with Epididymal Sperm Maturation and Motility.

Mammalian sperm contain the serine/threonine phosphatases PP1γ2 and PP2A. The role of sperm PP1γ2 is relatively well studied. Here we confirm the presence of PP2A in sperm and show that it undergoes marked changes in methylation (leucine 309), tyrosine phosphorylation (tyrosine 307) and catalytic activity during epididymal sperm maturation. Spermatozoa isolated from proximal caput, distal caput and caudal regions of the epididymis contain equal immuno-reactive amounts of PP2A. Using demethyl sensitive antibodies we show that PP2A is methylated at its carboxy terminus in sperm from the distal caput and caudal regions but not in sperm from the proximal caput region of the epididymis. The methylation status of PP2A was confirmed by isolation of PP2A with microcystin agarose followed by alkali treatment, which causes hydrolysis of protein carboxy methyl esters. Tyrosine phosphorylation of sperm PP2A varied inversely with methylation. That is, PP2A was tyrosine phosphorylated when it was demethylated but not when methylated. PP2A demethylation and its reciprocal tyrosine phosphorylation were also affected by treatment of sperm with L-homocysteine and adenosine, which are known to elevate intracellular S-adenosylhomocysteine, a feedback inhibitor of methyltransferases. Catalytic activity of PP2A declined during epididymal sperm maturation. Inhibition of PP2A by okadaic acid or by incubation of caudal epididymal spermatozoa with L-homocysteine and adenosine resulted in increase of sperm motility parameters including percent motility, velocity, and lateral head amplitude. Demethylation or pharmacological inhibition of PP2A also leads to an increase in phosphorylation of glycogen synthase kinase-3 (GSK3). Our results show for the first time that changes in PP2A activity due to methylation and tyrosine phosphorylation occur in sperm and that these changes may play an important role in the regulation of sperm function.

Quality Metrics in Surgery Resident Performance of Screening Colonoscopy.

In an attempt to further standardize surgical training, the American Board of Surgery now requires that residents provide evidence that they are certified in flexible endoscopy. This prospective study was designed to determine whether, through a structured curriculum, junior level residents could learn to conduct competent and safe screening colonoscopy (SC). An Institutional Review Board-approved prospective analysis of SC performed by five postgraduate year-2 residents during the 2012-2013 academic year was completed. All SC were performed under direct supervision of one of the two surgical endoscopists after each resident passed a structured endoscopy simulation curriculum. The following metrics of the American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology were recorded: bowel prep quality; cecal intubation; withdrawal time; number of visualized polyps; procedural duration; final pathology; adenoma detection rate (ADR); and, complications. Power analysis revealed that 108 procedures were required for an 80 per cent probability of data analysis accuracy. (American Society for Gastrointestinal Endoscopy ASGE/American College of Gastroenterology benchmark values in parentheses): 166 colonoscopies were performed, of which 149 met inclusion criteria. Bowel prep was considered "excellent" or "good" in 90 per cent of cases. The cecum was reached in 96 per cent of cases. Mean withdrawal time was 12 minutes (≥6 minute). Average procedure time was 30 minutes (≤ 30 minute). Polyp(s) were visualized and removed in 30 per cent of patients. The overall adenoma detection rate was 22.8 per cent (>20%). The ADR for males was 29.5 per cent (>25%). The ADR for females was 18.2 per cent (>15%). Average polyp size was 7.7 mm (range: 2-25 mm). No patients were readmitted for bleeding or perforation. Within a structured learning environment, trained surgical endoscopists can teach junior level surgery residents to perform safe and competent screening colonoscopy.

Dynamic multiplanar real time ultrasound guided infraclavicular subclavian vein catheterization.

Ultrasound guided vascular access has been well-characterized as a safe and effective technique for internal jugular and femoral vein catheterization. However, there is limited experience with the use of ultrasound to access the infraclavicular subclavian vein. Multiple ultrasound techniques do exist to identify the subclavian vein, but real time access is limited by vessel identification in a single planar view. To overcome this limitation, a novel technique of ultrasound guided infraclavicular subclavian vein catheterization using a real time multiplanar approach has been developed. The initial experience with this approach is described. A single surgeon used combined oblique, transverse, and longitudinal views along with Doppler color flow images to both define the infraclavicular anatomy and to obtain subclavian vein access in 42 adult patients (20 M/22 F and 22 L/20 R) with a mean body mass index of 29.2 (range = 18.9-55.4). Chest x-ray was obtained to confirm position and to rule out pneumothorax. Subclavian vein cannulation was achieved in 100 per cent of patients; subsequent catheterization was successful in 92.9 per cent. The number of attempts required for cannulation averaged 1.3 (range = 1-5), and decreased after a five patient learning curve. No patient developed a pneumothorax, hematoma, or cannula malposition. Ultrasound guided multiplanar infraclavicular subclavian vein access appears to be a safe and effective adjunct for central line placement.

Development of a web-based laparoscopic technical skills assessment and testing instrument: a pilot study.

OBJECTIVE: Current surgical training programs rely heavily on subjective assessments to measure operative proficiency, despite heavy emphasis on standardized testing as a means to rank scholastic ability. A compact laparoscopic simulator was developed with the intention to create a technical skill evaluation system that resembles standardized testing to provide the user with real-time percentile scores in a variety of skill metrics. The calculation of percentiles is only accurate if the pool of scores resembles a specific distribution (e.g., normal or log-normal distribution). We hypothesize that the grading measures provided by the simulator will follow normal or log-normal distributions. MATERIALS AND METHODS: A total of 29 surgical trainees with varying levels of laparoscopic experience were surveyed regarding their current training, proficiencies, and experience with the Fundamentals of Laparoscopic Surgery curriculum and then asked to perform a standard peg-transfer task 5 times. A proprietary device placed along the trocars of a laparoscopic box trainer was used to gather data that, when subjected to unique algorithms, gave real-time, web-based feedback to trainees on the following metrics: volume of instrument use, economy of movement, angular instrument path, instrument rotation, bimanual coordination, smoothness, time to task completion, and depth perception. Numerical data were plotted on a frequency histogram. Minitab software was used to identify if individual metrics fit a standard distribution curve. Analysis of variance was used to differentiate among 3 established physician skill levels, as a means of assessing construct validity. RESULTS: In the goodness-of-fit tests performed, angular path, depth perception, rotation, and smoothness were found to best fit a log-normal distribution (p > 0.1). Bimanual coordination was found to fit a normal distribution (p ≥ 0.067). However, both normal and log-normal distributions were rejected (p ≤ 0.01) for the metrics of time, volume, and economy of movement. After separating participants into 3 groups based on level of experience with the Fundamentals of Laparoscopic Surgery curriculum, analysis of variance showed significant differences among all group means across the 5 metrics (i.e., angular path, depth perception, rotation, smoothness, and bimanual coordination; p ≤ 0.023). CONCLUSION: A proprietary device provided quantitative assessment of laparoscopic skills, which can be used to differentiate among skill levels. Of the 8 tested metrics, 5 fit a normal or log-normal distribution, meaning the scores can statistically be ranked by percentile. Time, volume, and economy of movement did not fit desired distributions. The grading system proved to have construct validity, indicating it may be useful in the longitudinal assessment of laparoscopic skills of surgical trainees.

High-fidelity, low-cost, automated method to assess laparoscopic skills objectively.

BACKGROUND: We sought to define the extent to which a motion analysis-based assessment system constructed with simple equipment could measure technical skill objectively and quantitatively. METHODS: An "off-the-shelf" digital video system was used to capture the hand and instrument movement of surgical trainees (beginner level = PGY-1, intermediate level = PGY-3, and advanced level = PGY-5/fellows) while they performed a peg transfer exercise. The video data were passed through a custom computer vision algorithm that analyzed incoming pixels to measure movement smoothness objectively. RESULTS: The beginner-level group had the poorest performance, whereas those in the advanced group generated the highest scores. Intermediate-level trainees scored significantly (p < 0.04) better than beginner trainees. Advanced-level trainees scored significantly better than intermediate-level trainees and beginner-level trainees (p < 0.04 and p < 0.03, respectively). CONCLUSIONS: A computer vision-based analysis of surgical movements provides an objective basis for technical expertise-level analysis with construct validity. The technology to capture the data is simple, low cost, and readily available, and it obviates the need for expert human assessment in this setting.

Acceptability of an Online Health Videogame to Improve Diet and Physical Activity in Elementary School Students: "Fitter Critters"

OBJECTIVE: Interest in health videogames to stimulate health behavior change is increasing, yet little research exists on their use. This study tested the acceptability of an online health videogame called "Fitter Critters™" (Megazoid Games, Collegeville, PA) for improving healthy diet and activity in elementary school students. SUBJECTS AND METHODS: In October and November 2011, fifth grade students (n=97) from a school in central Massachusetts played the game for 1 week during their health class. Measures of nutrition and activity knowledge, attitudes, and self-efficacy were completed prior to playing the game and again on the final day along with a videogame acceptability questionnaire. RESULTS: The videogame was highly acceptable to participants as measured by the acceptability questionnaire mean rating of 4.52 (SD=0.60), where 1=strongly disagree and 5=strongly agree; 73% of students played the game at least once outside of class. Significant increases in positive attitudes toward healthy eating (P<0.001) and healthy eating self-efficacy (P=0.02) and marginally significant increases in nutrition knowledge (P=0.08) were observed. CONCLUSIONS: The "Fitter Critters" health videogame engages students in learning about healthy eating and activity. Further research should assess whether the positive changes observed in knowledge, attitudes, and self-efficacy translate into behavior change.

The effect of call on neurosurgery residents' skills: implications for policy regarding resident call periods.

OBJECT: Although fatigue and its effects on surgical proficiency have been an actively researched area, previous studies have not examined the effect of fatigue on neurosurgery residents specifically. This study aims to quantify the effect of fatigue on the psychomotor and cognitive skills of neurosurgery residents. METHODS: Seven neurosurgery residents performed a minimum of 3 and a maximum of 4 sessions of 6 surgical exercises precall and postcall. The simulation exercises were designed to measure a surgeon's cognitive abilities, such as memory and attention, while performing simulated surgical tasks and exercises that have been previously validated in several studies, including studies measuring the impact of fatigue on general surgery residents. Each exercise measured tool-movement smoothness, time elapsed, and cognitive errors. The change in surgical skills in precall and postcall conditions was assessed by means of an ANOVA, with p < 0.05 considered statistically significant. RESULTS: The neurosurgery residents did not show a statistically significant difference in their surgical skills between the pre- and postcall states (p < 0.3, p < 0.4, and p < 0.2 for movement smoothness, time elapsed, and cognitive errors, respectively). The mean decrement for all residents in the postcall condition was 13.1%. CONCLUSIONS: Postcall fatigue is associated with a marginal decrease in proficiency during simulated surgery in neurosurgery residents. In a similar study, general surgery residents showed a statistically significant decrement of 27.3% in the postcall condition. The impact of fatigue on different specialties should be further investigated prior to implementation of a national physician work-hour policy.

Honing a surgeon's decision making skills in the presence of mechanical tasks.

BACKGROUND: Although surgeons perform procedures and tasks under a significant amount of cognitive load, current simulators focus on training psychomotor skills in isolation. This may limit the transfer of learned skills to actual surgical environments. METHODS: Visuohaptic simulations were created that required participants to hone psychomotor skills in the presence of cognitive load. A control group (n = 7) trained on conventional skills simulator and their performance was compared with the experimental group (n = 7) in terms of learning curves and performance on a transfer task. RESULTS: The experimental group performed significantly better than the control group in terms of both learning curves and performance on the transfer task. CONCLUSIONS: Simulations that combine psychomotor and cognitive skills training are more effective than simulators that focus on psychomotor skills in isolation.

Impact of fatigue on neurophysiologic measures of surgical residents.

BACKGROUND: To gain additional insight into the impact of fatigue on surgery resident proficiency, we set out to quantify its impact on behavioral and neurophysiologic measures. STUDY DESIGN: Simulations were first created using a visio-haptic joystick attached to a surgical instrument (tool) that allows realistic interactions. Before baseline (pre-call) and after call, 7 PGY1 surgery residents performed simulation tasks that required varying levels of psychomotor and cognitive skill. Residents completed 3 sessions per week for 4 weeks. Surgical proficiency was established using 5 metrics: hand movement smoothness; instrument movement smoothness; time to task completion; gesture level proficiency and cognitive errors. Data (percent change from baseline, pre-call) were analyzed using repeated measures ANOVA. While performing these tasks, the residents also wore an EEG cap (B-Alert; Advanced Brain Monitoring), the data from which provided second to second insight into the effects of workload, distraction, and attention on task performance. Mean (±SD) pre-call and post-call values for each were analyzed using repeated measures ANOVA. RESULTS: Residents experienced significant (p < 0.014) post-call erosions in surgical proficiency, punctuated by dramatic increases in cognitive errors. EEG-based attention scores showed a significant (p < 0.014) concomitant decrement of 40%; distraction/drowsiness scores increased by 91%; and workload score increased by 51%. CONCLUSIONS: Fatigue adversely affects PGY1 resident surgical proficiency and neurophysiologic performance.

The validity of take-home surgical simulators to enhance resident technical skill proficiency.

BACKGROUND: It is unknown whether surgical residents who learn minimal-access surgery skills in an unstructured environment (ie, at home), will develop a technical skill set that rivals that of those trained in the more traditional, structured learning environment. METHODS: Seven surgery residents were provided structured learning through didactic and hands-on skills training sessions and consistent supervision throughout training. A second group of 7 residents participated in an unstructured learning curriculum of training without supervision. End points were determined at the end of training using a standardized simulator based on predetermined performance measures. RESULTS: Both groups achieved high task scores, with comparable scores on gesture proficiency, hand movement smoothness, instrument movement smoothness, errors, and time elapsed. There was no significant difference between group differences in final skills scores. CONCLUSIONS: Unstructured learning is equally effective in delivering quality skills training when compared with structured training.

Toward effective pediatric minimally invasive surgical simulation.

BACKGROUND/PURPOSE: Simulation is increasingly being recognized as an important tool in the training and evaluation of surgeons. Currently, there is no simulator that is specific to pediatric minimally invasive surgery (MIS). A fundamental technical difference between adult and pediatric MIS is the degree of motion scaling. Smaller instruments and areas of dissection under greater optical magnification require finer, more precise hand movements. We hypothesized that this can be used to detect differences in skills proficiency between pediatric and general surgeons. METHODS: We programmed a virtual reality simulation of intracorporeal suturing with modes that used motion scaling to mimic conditions of either adult or pediatric MIS. The participants consisted of pediatric and general surgeons who wore motion-sensing gloves. Metrics included time elapsed, penetration errors, tool movement smoothness, hand movement smoothness, and gesture level proficiency. RESULTS: For all measures, pediatric surgeons demonstrated superior proficiency on exercises conducted in pediatric conditions (P < .05). Performance in adult conditions was similar between the 2 groups. CONCLUSION: Pediatric surgeons possess unique skills compared with general surgeons that relate to the technical challenges they routinely face, reinforcing the need for a surgical simulator specific to pediatric MIS. This validates our simulator and the manipulation of motion scaling as a useful training tool.

Initial experiences in embedding core competency education in entry-level surgery residents through a nonclinical rotation.

BACKGROUND: Health care continues to expand in scope and in complexity. In this changing environment, residents are challenged with understanding its intricacies and the impact it will have on their professional activities and careers. AIM: Embedding each of the competency elements in residents in a meaningful way remains a challenge for many surgery residency program directors. METHODS: We established a nonclinical rotation to provide surgery postgraduate year-1 (PGY-1) residents with a structured, multifaceted, largely self-directed curriculum into which each of the 6 core competencies are woven. Posttesting strategies were established for most curricular experiences to ensure to the greatest possible extent that each resident will have achieved an acceptable level of understanding of each of the competency areas before being given credit for the rotation. RESULTS: By uniformly exceeding satisfactory scores on respective objective analyses, residents demonstrated an increased (at least short-term) understanding of each of the assessed competency areas. CONCLUSION: Our project sought to address a prior lack of opportunity for our residents to develop a sound foundation for our residents in systems-based practice. Our new rotation addresses systems-based practice in several different learning environments, including emergency medical service ride-along, sentinel event participation, and hospice visits. Several research projects have enhanced the overall learning program. Our experience shows that a rotation dedicated to competency training can provide an innovative and engaging means of teaching residents the value of each element.

Disparity between actual case volume and the perceptions of case volume needed to train competent general surgeons.

BACKGROUND: Variances between resident expectations and faculty expectations may create conflict and/or dissatisfaction. The objective of this study was to determine if resident expectations of case requirements differed significantly from faculty expectations and/or national and program averages. METHODS: Residents and faculty members from 3 separate residency programs in Phoenix were sent an electronic survey and asked to indicate the number of operations as surgeon that should be performed by a resident during surgical residency in 34 categories in order to be deemed a competent general surgeon. The faculty and resident responses were compared with the average number of cases performed by graduating residents in these Phoenix programs and national means for 2007-2008. RESULTS: The resident response rate was 65% (55 of 84) and the faculty response rate was 80% (37 of 46). Residents' responses of necessary numbers of cases exceeded program averages in 76% of categories and national averages in 73% of categories. Faculty perceptions of necessary numbers of cases exceeded both program and national averages in 65% of categories. The largest discrepancies for both residents and faculty were their perceptions of the number of necessary cases of nonoperative trauma compared with the national mean (responses were 307% and 193% more respectively) and the number of cases of laparoscopic cholecystectomy compared with actual program averages (responses were 57% and 63% less respectively). CONCLUSIONS: Resident and faculty perceptions of the number of cases needed for a competent graduating general surgery resident differ substantially from each other as well as from actual means. Improved education of each group to better align expectations with reality may improve satisfaction during training and confidence upon completion of training.

Quantitative evaluation of retention of surgical skills learned in simulation.

BACKGROUND: While initial results suggest that simulation does promote learning, there is a dearth of studies that define the extent to which skills learned through simulation are retained. METHODS: Residents skills were measured upon completion of an initial simulation training (baseline scores) and then every month for 6 months. Analysis was also performed to identify the number of iterations of practice required to regain baseline scores. RESULTS: While skill scores did not deteriorate from baseline after the first 3 months (p = 0.61, p = 0.44, p = 0.2, respectively), all scores (except time elapsed) reflected significant deterioration from the fourth month onward (p < 0.05, p < 0.032, p < 0.02). However the number of practice sessions required to regain baseline scores was significantly less than that required to achieve the baseline skill set (p < 0.0003). CONCLUSIONS: Skills learned through simulation show significant deterioration over long periods of time, suggesting that periodic retraining of skills may be necessary to maintain surgical proficiency.

Effects of duty hours and time of day on surgery resident proficiency.

BACKGROUND: Night floats have evolved in the era of limited resident work hours. This study was designed to define the effect of restricted nighttime duty hours on the psychomotor and cognitive skills of surgery residents. METHODS: To quantify the effect of fatigue on the skills of residents on day-shift and night-float rotations, residents were asked to complete visuohaptic simulations before and after 12-hour duty periods and to rate their fatigue level with questionnaires. RESULTS: Both groups showed significant decrements in proficiency measures after their shifts compared with baseline. The night-float group showed more significant declines (P < .05) in all areas assessed than the day-shift group. The night-float group was significantly less proficient in cognitive tasks after their shifts compared with the day-shift group. CONCLUSIONS: The deterioration of surgical proficiency is to a degree dependent on the time of day during which call occurs, not solely on the length of call.