Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis.

Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.

T/myeloid mixed phenotype acute leukaemia harbouring TLX3::BCL11B with TLX3 activation.

T/myeloid mixed phenotype acute leukaemia (MPAL) is a rare aggressive acute leukaemia with poorly understood pathogenesis. Herein, we report two cases of T/myeloid MPAL harbouring BCL11B-associated structural variants that activate TLX3 (TLX3::BCL11B-TLX3-activation) by genome sequencing and transcriptomic analyses. Both patients were young males with extramedullary involvement. Cooperative gene alterations characteristic of T/myeloid MPAL and T-lymphoblastic leukaemia (T-ALL) were detected. Both patients achieved initial remission following lineage-matched ALL-based therapy with one patient requiring a lineage-switched myeloid-based therapy. Our study is the first to demonstrate the clinicopathological and genomic features of TLX3::BCL11B-TLX3-activated T/myeloid MPAL and provide insights into leukaemogenesis.

Better operating room efficiency and reduced staff demand: Individualised versus off-the-shelf total knee arthroplasty.

PURPOSE: The purpose of this pilot cross-sectional study was to compare the operating room (OR) efficiency and intraoperative staff task load when performing individualised versus off-the-shelf (OTS) total knee arthroplasty (TKA). METHODS: A consecutive series of 28 patients randomised (1:1) to receive either OTS TKA or individualised TKA were included. The OR staff workload was assessed with the NASA Task Load Index (TLX), a subjective grading system assessing mental demand, physical demand, temporal demand, performance, effort and frustration on a scale from 0 (very low) to 20 (very high). The time for patient preparation, surgical time, closure and total OR time was recorded to assess OR efficiency. Effect sizes of differences between OTS and individualised TKA were expressed as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Patients in both cohorts were similar in age (OTS vs. individualised TKA (median [IQR]), 67 [63-76] vs. 71 [68-79]; p = 0.207) and body mass index (BMI) (29 [24-33] vs. 29 [26-31]; p = 0.807), and there were no significant differences in other preoperative characteristics. The OR staff perceived individualised TKA as less demanding than OTS TKA: Individualised TKA was rated significantly better across the six domains of the NASA TLX: mental demand by 5.6 points, physical demand by 6.3 points, temporal demand by 5.3 points, performance by 3.6 points, effort by 5.9 points and frustration by 5.8 points. Individualised TKA resulted in statistically significantly shorter mean total OR time (MD, 10 min; p = 0.018). CONCLUSION: The staff in the OR found that individualised TKA is less mentally, physically and temporally demanding than OTS TKA. The average total time spent in the OR during individualised TKA is 10 min less than during OTS TKA. CLINICAL TRIAL REGISTRATION: This study constitutes a part of a larger registered randomised controlled trial comparing patient satisfaction following OTS versus individualised TKA (NCT04460989). LEVEL OF EVIDENCE: Level III.

Evaluating User Perceptions of a Vibrotactile Feedback System in Trunk Stabilization Exercises: A Feasibility Study.

Low back pain patients often have deficits in trunk stability. For this reason, many patients receive physiotherapy treatment, which represents an enormous socio-economic burden. Training at home could reduce these costs. The problem here is the lack of correction of the exercise execution. Therefore, this feasibility study investigates the applicability of a vibrotactile-controlled feedback system for trunk stabilisation exercises. A sample of 13 healthy adults performed three trunk stabilisation exercises. Exercise performance was corrected by physiotherapists using vibrotactile feedback. The NASA TLX questionnaire was used to assess the practicability of the vibrotactile feedback. The NASA TLX questionnaire shows a very low global workload 40.2 [29.3; 46.5]. The quality of feedback perception was perceived as good by the subjects, varying between 69.2% (anterior hip) and 92.3% (lower back). 80.8% rated the feedback as helpful for their training. On the expert side, the results show a high rating of movement quality. The positive evaluations of the physiotherapists and the participants on using the vibrotactile feedback system indicate that such a system can reduce the trainees fear of independent training and support the users in their training. This could increase training adherence and long-term success.

Validation and effect of the NASA-TLX score on the assessment of the workload of pediatric robotic operations.

OBJECTIVE: The objective of the study was to assess the validity of the NASA-TLX score in rating the workload of pediatric robotic operations. METHODS: The workload of 230 pediatric gastrointestinal and thoracic robotic operations was rated using the NASA-TLX score. The difference between the high workload group and the low workload group in each subscale of the NASA-TLX score was analyzed. The correlation of each subscale with the total workload score in the high workload group and low workload group was also analyzed. A logistic regression analysis was subsequently conducted to assess the effects of different factors (sex, age, weight, procedure duration, procedure specialties, combined malformation and blood loss) on the workload. RESULTS: The average NASA-TLX score was 56.5 ± 5.1 for the total group, 56.9 ± 5.0 for the gastrointestinal group and 54.6 ± 4.8 for the thoracic group, p = 0.007. The score of the high workload group was 62.7 ± 3.2, while it was 50.6 ± 2.7 for the low workload group (p < 0.001). The score on each subscale was also significantly different between the high and low workload groups. In the high workload group, a stronger correlation was observed between the total score and TD and Fr and a lower correlation with MD and Pe. In the low workload group, all six subscales showed a moderate correlation with the total score. A multivariate logistic regression analysis revealed that the procedure duration was an independent influencing factor for a higher workload score. CONCLUSIONS: NASA-TLX is a valid tool to rate the surgeon's workload in pediatric robotic surgery. A longer operative time contributes to a higher workload.

Stress and Workload Assessment in Aviation-A Narrative Review.

In aviation, any detail can have massive consequences. Among the potential sources of failure, human error is still the most troublesome to handle. Therefore, research concerning the management of mental workload, attention, and stress is of special interest in aviation. Recognizing conditions in which a pilot is over-challenged or cannot act lucidly could avoid serious outcomes. Furthermore, knowing in depth a pilot's neurophysiological and cognitive-behavioral responses could allow for the optimization of equipment and procedures to minimize risk and increase safety. In addition, it could translate into a general enhancement of both the physical and mental well-being of pilots, producing a healthier and more ergonomic work environment. This review brings together literature on the study of stress and workload in the specific case of pilots of both civil and military aircraft. The most common approaches for studying these phenomena in the avionic context are explored in this review, with a focus on objective methodologies (e.g., the collection and analysis of neurophysiological signals). This review aims to identify the pros, cons, and applicability of the various approaches, to enable the design of an optimal protocol for a comprehensive study of these issues.

Structural basis for corepressor assembly by the orphan nuclear receptor TLX.

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.

Quantitative and qualitative workload assessment in steep terrain forest operations: fostering a safer work environment through yarder automation.

Many forestry roles have changed from being manual tasks with a high physical workload to being a machine operator task with a high mental workload. Automation can support a decrease in mental fatigue by removing tasks that are repetitive and monotonous for the operators. Cable yarding presents an ideal opportunity for early adoption of automation technology; specifically the carriage movement along a defined corridor. A Valentini V-850 cable yarder was used in an Italian harvesting setting, in order to gauge the ergonomic benefit of carriage control automation. The study showed that automating yarder carriage movements improved the ergonomic situation of the workers directly involved in the related primary tasks. However, the caveat is that improving one work task may negatively affect the other work tasks, and therefore introducing automation to a worksite must be done after considering all impacts on the whole system. Practitioner summary: Automation decreased the winch operator's mental workload while improving overall productivity. At the same time, the mental and physiological workload of the operator tasked with bucking were slightly increased. Ideally, winch automation should be coupled with bucking mechanisation to balance the intervention and boost both operator well-being and productivity.

Impaired generation of mature neurons due to extended expression of Tlx by repressing Sox2 transcriptional activity.

As a master regulator of the dynamic process of adult neurogenesis, timely expression and regulation of the orphan nuclear receptor Tailless (Tlx) is essential. However, there is no study yet to directly investigate the essential role of precise spatiotemporal expressed Tlx. Here, we generated a conditional gain of Tlx expression transgenic mouse model, which allowed the extended Tlx expression in neural stem cells (NSCs) and their progeny by mating with a TlxCreERT2 mouse line. We demonstrate that extended expression of Tlx induced the impaired generation of mature neurons in adult subventricular zone and subgranular zone. Furthermore, we elucidated for the first time that this mutation decreased the endogenous expression of Sox2 by directly binding to its promoter. Restoration experiments further confirmed that Sox2 partially rescued these neuron maturation defects. Together, these findings not only highlight the importance of shutting-off Tlx on time in controlling NSC behavior, but also provide insights for further understanding adult neurogenesis and developing treatment strategies for neurological disorders.

Comparison of three-dimensional (3D) endovision system versus ultra-high-definition 4K endovision system in minimally invasive surgical procedures: a randomized-open label pilot study.

BACKGROUND: Experimental work comparing 3-Dimensional (3D) and 4K ultra-high-definition endovision system (4K) indicates that the latter with double the resolution of standard 2D high-definition systems may provide additional visual cues to compensate for the lack of stereoscopic vision. There is paucity of studies comparing 3D and 4K system in clinical settings. This randomized study compares 3D and 4K systems in three laparoscopic procedures of increasing complexity. METHODS: 139 patients undergoing laparoscopic cholecystectomy (60 patients), transabdominal preperitoneal (TAPP) repair (49 patients) and laparoscopic Heller's cardiomyotomy with anti- reflux procedure (30 patients) between May 2018 and February 2020 were randomized to undergo surgery using either 3D or 4K systems. Primary objective was to measure total operative time. Secondary objectives were to compare workload perceived by surgeons using SURG-TLX and surgeon satisfaction score. Timings of key surgical steps and peri-operative course of the patients was also recorded. Data were analyzed using Stata Corp. 2015. RESULTS: Patients undergoing surgery with 3D and 4K systems were comparable in their clinical and demographic profiles. The mean total operative time in 3D and 4K groups was comparable in cholecystectomy (52.7 vs 56.2, p = 0.50), TAPP (63.8 vs 69.6, p = 0.25) and Heller's cardiomyotomy (124.7 vs 143.3, p = 0.14) with faster hiatal dissection in 3D group (8 min, p = 0.02). Operative time was better in patients undergoing Heller's myotomy with Angle of His accentuation with 3D by 28 min (p = 0.03). Total workload was similar in 3D and 4K groups in all the procedures but mental & physical demand was lower in 3D group in Heller's cardiomyotomy (p = 0.03, p = 0.01), Surgeon satisfaction score was comparable in all three procedures. CONCLUSION: Overall, 3D HD and 4K systems are comparable in performing laparoscopic cholecystectomy, TAPP and Heller's Cardiomyotomy. Hiatal dissection time, mental and physical task load was better with 3D in Heller's Cardiomyotomy.

Exploring the Peak-End Effects in Air Traffic Controllers' Mental Workload Ratings.

OBJECTIVE: This study examined whether professional air traffic controllers (ATCos) were subject to peak-end effects in reporting their mental workload after performing an air traffic control task, and in predicting their mental workload in future scenarios. BACKGROUND: In affective experience studies, people's evaluation of a period of experience is strongly influenced by the most intense (peak) point and the endpoint. However, whether the effects exist in mental workload evaluations made by professional operators is still not known. METHOD: In Study 1, 20 ATCos performed air traffic control scenarios on high-fidelity radar simulators and reported their mental workload. We used a 2 (high peak, low peak) × 2 (high end, low end) within-subject design. In Study 2, another group of 43 ATCos completed a survey asking them to predict their mental workload given the same air traffic control scenarios. RESULTS: In Study 1, ATCos reported higher mental workload after completing the high-peak and the high-end scenarios. In contrast, in Study 2, ATCos predicted the peak workload effect but not the end workload effect when asked to predict their experience in dealing with the same scenarios. CONCLUSION: Peak and end effects exist in subjective mental workload evaluation, but experts only had meta-cognitive awareness of the peak effect, and not the end effect. APPLICATION: Researchers and practitioners that use subjective workload estimates for work design decisions need to be aware of the potential impact of peak and end task demand effects on subjective mental workload ratings provided by expert operators.

Study protocol: a multicenter randomized controlled trial of the multifaceted workload reduction of the anti-adhesion barrier for diverting ileostomy in laparoscopic rectal surgery, YCOG 2005 (ADOBARRIER study).

BACKGROUND: There are few randomized controlled trials on the efficacy of spray-type anti-adhesion material during diverting ileostomy in laparoscopic rectal cancer surgery. PURPOSE: This study will assess whether or not spraying an anti-adhesion material during diverting ileostomy could reduce the surgeon's multifaceted workload in ileostomy closure. METHODS: Patients with laparoscopic or robotic surgery for rectal cancer scheduled for low anterior resection and diverting ileostomy will be enrolled in the ADOBARRIER study (multicenter, single-blind, randomized controlled trial). The target sample size is set at 120 cases, which will be randomly divided into an anti-adhesion material-using group and a non-using group at a ratio of 1:1. The primary endpoint is the multifaceted workload of the surgeon of ileostomy closure using SURG-TLX between groups with and without usage of the anti-adhesion material during diverting ileostomy construction; the secondly endpoint is the operative time, amount of intraoperative blood loss, degree of adhesions, and extent of intra-abdominal adhesions when the ileostomy is closed. CONCLUSIONS: This RCT will evaluate the efficacy and safety of spray-type anti-adhesion material for diverting ileostomy construction. The results of this study are expected to facilitate decision-making regarding the use of anti-adhesion material. TRIAL REGISTRATION: This trial was registered with the Japan Registry of Clinical Trials (jRCT) in October 2020 as jRCTs032200155.

Comparison of two-dimensional high-definition, ultra high-definition and three-dimensional endovision systems: an ex-vivo randomised study.

BACKGROUND: Two-dimensional high-definition (2D HD) endovision system is preferred for laparoscopic surgery. Recently, new generation three-dimensional (3D) HD and ultra-HD (4K) endovision systems are introduced to improve the safety and efficacy of laparoscopic surgery. There is limited evidence on superiority of one technology over the others. This experimental trial was designed to evaluate 2D HD, 3D HD and 4K HD endovision systems in performance of standardized tasks. METHODS: This was a randomized, cross-over experimental study. Twenty-one surgical residents who were exposed to laparoscopic surgery were enrolled. Participants were randomly assigned into three groups. Each group performed standardised tasks i.e. peg transfer, precision cutting, navigating in space and intra-corporeal suturing using 2D HD, 4K HD and 3D HD endovision systems on a box trainer. Procedures were recorded as 2D HD videos and analysed later. Participant's perceived workload was assessed using Surg-TLX questionnaire. Primary endpoints were execution time in seconds and error score. Secondary endpoint was workload assessment. RESULTS: The 3D HD had shorter execution time compared to 2D HD and 4K HD in all tasks except precision cutting (p = 0.004, 0.03, 0.001, 0.001 and p = 0.002, 0.191, 0.006, 0.005 in peg transfer, precision cutting, navigating in space and intra-corporeal suturing respectively). The 4K HD was significantly faster than 2D HD only in navigating in space task (p = 0.002). The error score between 3D HD and 4K HD were comparable in all tasks. The 2D HD had significantly more error scores compared to 4K HD, 3D HD in peg transfer task (p = 0.005, 0.014, respectively). 3D HD had significantly less workload than 2D HD and 4K HD in most of the dimensions of Surg-TLX CONCLUSIONS: 3D HD endovision system in comparison to 2D HD and 4K HD, may lead to faster execution without compromising safety of a task and is associated with less workload.

Has COVID-19 changed the workload for primary care physicians? The case of Spain.

BACKGROUND: The COVID-19 pandemic has led to a massive over-exertion of doctors, multiplying their work intensity, overload and stress. Yet no studies have been conducted on the changes in primary care physician overload during the pandemic. OBJECTIVE: To address this research gap, the aim of this article is to document the subjective dimensions of physicians' work during the peak of the pandemic for comparison with a pre-COVID-19 situation. In addition, the relationship between workload and the individual characteristics of the physician or the percentage of tele-assistance is examined. METHODS: This study performs a subjective measurement procedure for the analysis of work overload through the NASA-TLX questionnaire, with a total of 102 records from 16 doctors from a Primary Health Centers of the Granada-Metropolitan Health district (Andalusia, Spain). RESULTS: The results reflect a significantly higher workload during COVID-19 in relation to a previous situation (66.1% versus 48.6% before COVID-19). All the dimensions of the NASA-TLX test suffered an increase during the COVID-19, this increase being higher in the physical, temporal and frustration levels. Interestingly, the findings reflect the higher the percentage of telematic consultations, the lower workload. CONCLUSIONS: Work overload and the emotional state of health workers is one of the many repercussions of the COVID-19 pandemic. The results derived from this study may be useful in formulating policies and practices related to the workforce development, funding streams to prepare for the next wave of COVID-19 infections as well as for future public health emergencies.

Reference values and subscale patterns for the task load index (TLX): a meta-analytic review.

The Task Load Index (TLX) is the predominant instrument for self-reporting workload. On the basis of a meta-analytic review of 556 studies, this paper supplies reference values for TLX and its six subscales across domains, technologies, regions, and real-life/lab settings. Across domains, TLX spans mean values from 35 for leisure to 56 for manual labour. TLX tends to be driven upward by the subscales of mental demand and effort and downward by the subscales of physical demand and frustration. For technologies, handheld devices are associated with lower TLX, possibly because they are simpler and more task-specific. TLX also varies across regions in that it is higher for studies in Asia than in Europe and North America. This variation is only partly explained by co-variation in domains. Furthermore, TLX is higher and its subscales more inter-correlated when it is studied in real-life rather than lab settings. Practitioner summary: Practitioners can use the reference values supplied in this paper to benchmark their TLX measurements against those from the corpus of TLX research. Furthermore, the reported subscale patterns add to the diagnostic power of the TLX instrument. Abbreviations: TLX: task load index; MD: mental demand; PD: physical demand; TD: temporal demand; EF: effort; PE: performance; FR: frustration.

Resting Cardiac Vagal Tone is Associated with Long-Term Frustration Level of Mental Workload: Ultra-short Term Recording Reliability.

Excessive mental workload represent a critical risk factor for workplace accidents. Heart rate variability (HRV) is a non-invasive low cost electrophysiological autonomic biomarker related to emotional and cognitive regulation. Several studies report that mental overload impairs parasympathetic-mediated HRV indices (e.g. rMSSD). However, the influence of resting state HRV as a predictor of long-term mental workload impairments remains unknown. Thirty participants (22 males; 8 females) had their HRV measured (5-min period) before performing the number search task. After the task, the mental load was accessed by the NASA-TLX questionnaire. A simple linear regression model between HRV and NASA-TLX dimensions showed that resting state rMSSD is associated to physical demand (ND-2, R2 = 0.143, p = 0.03) and frustration level (ND-6, R2 = 0.175, p = 0.02) dimensions of mental workload. The comparison between 1 and 5-min epochs suggests that regression models remain reliable even using the ultra-short term HRV (< 1 min) recording values (R2 values from 0.11 to 0.15 for ND-2 and R2 values from 0.16 to 0.19 for ND-6). These results suggest that resting state HRV is associated to long-term effects of mental workload on physical and emotional demands. In addition, the ultra-short term HRV indices remains reliable to assess ND-2 and ND-6 dimensions of mental workload when compared to gold-standard time interval (> 5 min). The resting state cardiac autonomic tone assessment optimizes the physiological approach with a quick, non-invasive and low-cost assessment that can provide insights about mental load adjustments to prevent work-related accidents.

How does physical guidance affect motor learning and learner's workload?

[Purpose] Physical guidance is routinely used in clinical practices such as rehabilitation to facilitate motor learning. Physical guidance would facilitate motor learning and reduce the workload; however, this relationship is unknown. Thus, we aimed to investigate this relationship using a physical guidance device. [Participants and Methods] Twenty-seven healthy young adults were randomly assigned to three groups and underwent varying practice conditions. The participants used a physical guidance device during practice for 2 days, did not use the device during practice for 2 days, or used the device on the first but not the second practice day. Motor learning was assessed by measuring the instability generated by the participants while maintaining a standing position on the Biodex Balance System. Psychological status was evaluated by analyzing the participants' responses to the National Aeronautics and Space Administration-Task Load Index. [Results] Improved performance was noted in all participants; however, those who used a physical guidance device during practice for 2 days exhibited poor motor learning compared with those assigned to the other two conditions. Frustration was significantly lower in participants who used a physical guidance device during practice than those who did not. [Conclusion] The use of physical guidance during practice can reduce participant frustration, but excessive physical guidance during practice reduces learning efficiency.

Nuclear receptor TLX regulates islet beta cell proliferation via E2F6.

Both type 1 and type 2 diabetes are associated with loss of functional beta cell mass, and strategies to restore beta cells are urgently needed. We reported previously that overexpression of the nuclear receptor TLX induces beta cell proliferation, but the underlying molecular mechanism has not been defined. Here, we identified direct targets of TLX in beta cells at the genome-wide level by ChIP-Seq. These targets include a cadre of regulators that are known to be critical for proliferation. Among these ChIP targets, E2F6 was tightly associated with the cell cycle modules, and thus, we further analyzed E2F6 expression and function in beta cells. We showed that E2F6 is strongly downregulated by TLX, and its expression inhibits beta cell proliferation. Moreover, coexpression of E2F6 with TLX partially abrogated the proliferative effects of TLX. These results strongly suggest that TLX acts through E2F6 to regulate beta cell proliferation. Together, the results of this study reveal a direct interaction between TLX and E2F6 and suggest new targets for the expansion of functional beta cell mass.

Congenital asplenia due to a tlx1 mutation reduces resistance to Aeromonas hydrophila infection in zebrafish.

It is documented that tlx1, an orphan homeobox gene, plays critical roles in the regulation of early spleen developmental in mammalian species. However, there is no direct evidence supporting the functions of tlx1 in non-mammalian species, especially in fish. In this study, we demonstrated that tlx1 is expressed in the splenic primordia as early as 52 hours post-fertilization (hpf) in zebrafish. A tlx1-/- homozygous mutant line was generated via CRISPR/Cas9 to elucidate the roles of tlx1 in spleen development in zebrafish. In the tlx1-/- background, tlx1-/- cells persisted in the splenic primordia until 52 hpf but were no longer detectable after 53 hpf, suggesting perturbation of early spleen development. The zebrafish also exhibited congenital asplenia caused by the tlx1 mutation. Asplenic zebrafish can survive and breed normally under standard laboratory conditions, but the survival rate of animals infected with Aeromonas hydrophila was significantly lower than that of wild-type (WT) zebrafish. In asplenic zebrafish, the mononuclear phagocyte system was partially impaired, as demonstrated by retarded b7r expression and reduced ccr2 expression after injection with an inactivated A. hydrophila vaccine. Furthermore, the expression of MHCII/IgM was significantly reduced in the congenitally asplenic fish compared with that of the WT zebrafish. Taken together, our data suggest that tlx1 is a crucial regulator of spleen development in fish, as it is in mammals. We have also provided a new perspective for studying the role of the spleen during pathogen challenge in fish.

The effect of repeated full immersion simulation training in ureterorenoscopy on mental workload of novice operators.

BACKGROUND: Difficult surgical procedures may result in a higher mental workload, leading to increased fatigue and subsequent errors. This study was aimed to investigate the effect of repeated simulation training in ureterorenoscopy in a high-fidelity setting on the performance and mental workload of novice operators. METHODS: Medical students voluntarily participated in the present simulation study. After a didactic and video-based lecture, they underwent simulation training involving a renal stone case, including a rigid cystoscope component (task 1, performing a WHO checklist, assembling a scope, and insertion of a guide-wire and an access sheath after examining the bladder) and a flexible ureterorenoscope component (task 2, retrieving a stone located in the upper calyx using a basket after inspecting the upper, middle, and lower calyx). Training was performed in a mock operating theater. Technical skills were assessed by one author (an experienced urologist) onsite using an Objective Structured Assessment of Technical Skills (OSATS) score at each training session. The mental workload was subjectively evaluated by the National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire after each training session. RESULTS: Seventeen students completed a minimum of 6 training sessions (male: female = 10: 7, median age of 22) over a median of 21 days (range, 10-32). In both tasks 1 and 2, the OSATS score improved over the 6 sessions with evidence of plateauing (MANOVA model, task 1: p < 0.0001, task 2: p < 0.0001). In contrast, the NASA-TLX score persistently decreased without plateauing (task 1: p = 0.0005, task 2: p = 0.0028). CONCLUSIONS: Under repeated simulation training in ureterorenoscopy in a high-fidelity setting, participants showed a continual decrease of the mental workload, while the improvement of technical skills reached a plateau over the 6 sessions. Our study showed the important benefit of simulation training to reduce the mental workload by repeated scenario training before actual clinical practice.