Turnover of Variant Surface Glycoprotein in Trypanosoma brucei Is Not Altered in Response to Specific Silencing.

African trypanosomes evade the immune system of the mammalian host by the antigenic variation of the predominant glycosylphosphatidylinositol (GPI)-anchored surface protein, variant surface glycoprotein (VSG). VSG is a very stable protein that is turned over from the cell surface with a long half-life (~26 h), allowing newly synthesized VSG to populate the surface. We have recently demonstrated that VSG turnover under normal growth is mediated by a combination of GPI hydrolysis and direct shedding with intact GPI anchors. VSG synthesis is tightly regulated in dividing trypanosomes, and when subjected to RNA interference (RNAi) silencing, cells display rapid cell cycle arrest in order to conserve VSG density on the cell surface (K. Sheader, S. Vaughan, J. Minchin, K. Hughes, et al., Proc Natl Acad Sci U S A 102:8716-8721, 2005, https://doi.org/10.1073/pnas.0501886102). Arrested cells also display an altered morphology of secretory organelles-engorgement of the trans-Golgi cisternae-that may reflect a disruption of post-Golgi secretory transport. We now ask whether trypanosomes under VSG silencing also reduce the rate of VSG turnover to further conserve coat density. Our data indicate that trypanosomes do not regulate VSG turnover according to VSG protein abundance, nor was there any effect on the post-Golgi transport of soluble or GPI-anchored secretory cargo. However, the surface morphology of silenced cells was altered from a typically rugose topology to a smoother profile, consistent with reduced overall membrane trafficking to the cell surface. IMPORTANCE African trypanosomes evade the host immune system by altering the expression of variant surface glycoproteins (VSGs) in a process called antigenic variation. VSG is essential, and when its synthesis is ablated by RNAi silencing, cells enter precytokinesis growth arrest as a means to maintain constant cell surface VSG levels. We have investigated whether arrested cells also alter the rate of natural VSG turnover as a means to conserve the surface coat. This work provides insights into the natural biology of the glycocalyx of this important human and veterinary parasite.

Stage-Specific COPII-Mediated Cargo Selectivity in African Trypanosomes.

A hallmark of eukaryotic cells is the ability to form a secretory pathway connecting many intracellular compartments. In the early secretory pathway, coated protein complex II (COPII)-coated vesicles mediate the anterograde transport of newly synthesized secretory cargo from the endoplasmic reticulum to the Golgi apparatus. The COPII coat complex is comprised of an inner layer of Sec23/Sec24 heterodimers and an outer layer of Sec13/Sec31 heterotetramers. In African trypanosomes, there are two paralogues each of Sec23 and Sec24, that form obligate heterodimers (TbSec23.2/TbSec24.1, TbSec23.1/TbSec24.2). It is not known if these form distinct homotypic classes of vesicles or one heterotypic class, but it is known that TbSec23.2/TbSec24.1 specifically mediate forward trafficking of GPI-anchored proteins (GPI-APs) in bloodstream-form trypanosomes (BSF). Here, we showed that this selectivity was lost in insect procyclic stage parasites (PCF). All isoforms of TbSec23 and TbSec24 are essential in PCF parasites as judged by RNAi knockdowns. RNAi silencing of each subunit had equivalent effects on the trafficking of GPI-APs and p67, a transmembrane lysosomal protein. However, silencing of the TbSec23.2/TbSec24.1 had heterodimer had a significant impact on COPII mediated trafficking of soluble TbCatL from the ER to the lysosome. This finding suggests a model in which selectivity of COPII transport was altered between the BSF and PCF trypanosomes, possibly as an adaptation to a digenetic life cycle. IMPORTANCE African trypanosomes synthesize dense surface coats composed of stage-specific glycosylphosphatidylinositol lipid anchored proteins. We previously defined specific machinery in bloodstream stage parasites that mediate the exit of these proteins from the endoplasmic reticulum. Here, we performed similar analyses in the procyclic insect stage and found significant differences in this process. These findings contribute to our understanding of secretory processes in this unusual eukaryotic model system.

Functional mechanisms of MYRF DNA-binding domain mutations implicated in birth defects.

Myrf is a pleiotropic membrane-bound transcription factor that plays critical roles in diverse organisms, including in oligodendrocyte differentiation, embryonic development, molting, and synaptic plasticity. Upon autolytic cleavage, the Myrf N-terminal fragment enters the nucleus as a homo-trimer and functions as a transcription factor. Homo-trimerization is essential for this function because it imparts DNA-binding specificity and affinity. Recent exome sequencing studies have implicated four de novo MYRF DNA-binding domain (DBD) mutations (F387S, Q403H, G435R, and L479V) in novel syndromic birth defects involving the diaphragm, heart, and the urogenital tract. It remains unknown whether and how these four mutations alter the transcription factor function of MYRF. Here, we studied them by introducing homologous mutations to the mouse Myrf protein. We found that the four DBD mutations abolish the transcriptional activity of the Myrf N-terminal fragment by interfering with its homo-trimerization ability by perturbing the DBD structure. Since the Myrf N-terminal fragment strictly functions as a homo-trimer, any loss-of-function mutation has the potential to act as a dominant negative. We observed that one copy of Myrf-F387S, Myrf-Q403H, or Myrf-L479V, but not Myrf-G435R, was tolerated by the Myrf N-terminal homo-trimer for structural and functional integrity. These data suggest that F387S, Q403H, and L479V cause birth defects by haploinsufficiency, while G435R does so via dominant negative functionality.

Knowledge, attitude and practice of the Sudanese people towards COVID-19: an online survey.

BACKGROUND: The Novel Corona virus SARS-CoV-2 emerged to affect the human population in 2019 causing COVID-19 pandemic. The only preventive measures available are social distancing, hand washing and face masks. This study aims to assess the knowledge, attitude and practice of the Sudanese people towards COVID-19. METHODS: An online cross-sectional study targeting adult Sudanese people was conducted in April 2020. The study used a self-administered questionnaire containing 18 knowledge questions, 5 questions for attitude and six questions for practices. Social media such as Facebook and WhatsApp were utilized to disseminate the questionnaire. The total number of eligible questionnaires available for analysis by the end of the period was 987. RESULTS: The mean (±SD) age of respondents was 30.13 (±9.84) years with males representing 55.4%. The majority were university and higher education levels (95.2%), residing in Khartoum (71.7%). The mean (±SD) knowledge score of the participants was 15.33 (± 2.24) and was found to be associated with education level and age groups (p-value = 0.022, P value =0.010) respectively. The mean (±SD) attitude score was 04.15 (± 0.97) and was significantly associated with older groups and better-educated participants (p-value =0.001, p-value = 0.048) respectively. The practices related to COVID-19 preventive measures mean (±SD) was 02.58 (± 1.73) with a significant difference between age groups and area of residence. CONCLUSIONS: This study showed that the participants had good knowledge and satisfactory attitude that was not similarly expressed into practice. Efforts are needed in health education and law enforcement to improve the practices among all groups with special emphasis on younger and less educated males.

Female Genital Cutting and Deinfibulation: Applying the Theory of Planned Behavior to Research and Practice.

At least 200 million girls and women across the world have experienced female genital cutting (FGC). International migration has grown substantially in recent decades, leading to a need for health care providers in regions of the world that do not practice FGC to become knowledgeable and skilled in their care of women who have undergone the procedure. There are four commonly recognized types of FGC (Types I, II, III, and IV). To adhere to recommendations advanced by the World Health Organization (WHO) and numerous professional organizations, providers should discuss and offer deinfibulation to female patients who have undergone infibulation (Type III FGC), particularly before intercourse and childbirth. Infibulation involves narrowing the vaginal orifice through cutting and appositioning the labia minora and/or labia majora, and creating a covering seal over the vagina with appositioned tissue. The WHO has published a handbook for health care providers that includes guidance in counseling patients about deinfibulation and performing the procedure. Providers may benefit from additional guidance in how to discuss FGC and deinfibulation in a manner that is sensitive to each patient's culture, community, and values. Little research is available to describe decision-making about deinfibulation among women. This article introduces a theoretically informed conceptual model to guide future research and clinical conversations about FGC and deinfibulation with women who have undergone FGC, as well as their partners and families. This conceptual model, based on the Theory of Planned Behavior, may facilitate conversations that lead to shared decision-making between providers and patients.

Parental attitudes and decisions regarding MMR vaccination during an outbreak of measles among an undervaccinated Somali community in Minnesota.

Incidence of measles is increasing in the US, largely due to transmission among growing unvaccinated communities. To elucidate predictors of parental decision to obtain measles, mumps, and rubella (MMR) vaccine for unvaccinated children during a measles outbreak, we surveyed families among a vaccine-hesitant Somali community in Minnesota. The survey assessed attitudes and beliefs about MMR vaccine, motivators for vaccinating, and intention to vaccinate future children on time. Among 300 families surveyed, 95% vaccinated their child with MMR due to fear of measles. The predominating parental concern about MMR vaccine (71%) was a fallacious presumed connection between vaccination and autism. Only 41% of parents intended to vaccinate future children on time with MMR; parents who received recommendations for MMR vaccination from multiple sources were more likely than other parents to intend to do so. These findings support the importance of diverse outreach efforts to increase vaccine coverage among undervaccinated communities.

Clitoral Reconstruction After Female Genital Mutilation/Cutting: A Review of Surgical Techniques and Ethical Debate.

INTRODUCTION: Clitoral reconstruction (CR) is a controversial surgical procedure performed for women who have undergone medically unnecessary, often ritualistic genital cutting involving the clitoris. Such cutting is known by several terms; we will use female genital mutilation/cutting (FGM/C). Treatments offered to women affected by complications of FGM/C include defibulation (releasing the scar of infibulation to allow penetrative intercourse, urinary flow, physiological delivery, and menstruation) and CR to decrease pain, improve sexual response, and create a pre-FGM/C genital appearance. AIM: In this study, our aim is to summarize the medical literature regarding CR techniques and outcomes, and stimulate ethical discussion surrounding potential adverse impacts on women who undergo the procedure. METHODS: A broad literature review was carried out to search any previous peer-reviewed publications regarding the techniques and ethical considerations for CR. MAIN OUTCOME MEASURE: The main outcome measure includes benefits, risks, and ethical analysis of CR. RESULTS: While we discuss the limited evidence regarding the risks and efficacy of CR, we did not find any peer-reviewed reports focused on ethical implications to date. CLINICAL IMPLICATIONS: CR can be indicated as a treatment for pain and potential improvement of associated sexual dysfunction when these have not responded to more conservative measures. Women must be appropriately informed about the risks of CR and the lack of strong evidence regarding potential benefits. They must be educated about their genital anatomy and disabused of any myths surrounding female sexual function as well as assessed and treated in accordance with the current scientific evidence and best clinical practices. STRENGTH & LIMITATIONS: This is the first formal ethical discussion surrounding CR. This is not a systematic review, and the ethical discussion of CR has only just begun. CONCLUSION: We present a preliminary ethical analysis of the procedure and its potential impact on women with FGM/C. Sharif Mohamed F, Wild V, Earp BD, et al. Clitoral Reconstruction After Female Genital Mutilation/Cutting: A Review of Surgical Techniques and Ethical Debate. J Sex Med 2020;17:531-542.

Functional mechanism and pathogenic potential of MYRF ICA domain mutations implicated in birth defects.

Myrf is a membrane-bound transcription factor that plays a key role in various biological processes. The Intramolecular Chaperone Auto-processing (ICA) domain of Myrf forms a homo-trimer, which carries out the auto-cleavage of Myrf. The ICA homo-trimer-mediated auto-cleavage of Myrf is a prerequisite for its transcription factor function in the nucleus. Recent exome sequencing studies have implicated two MYRF ICA domain mutations (V679A and R695H) in a novel syndromic form of birth defects. It remains unknown whether and how the two mutations impact the transcription factor function of Myrf and, more importantly, how they are pathogenic for congenital anomalies. Here, we show that V679A and R695H cripple the ICA domain, blocking the auto-cleavage of Myrf. Consequently, Myrf-V679A and Myrf-R695H do not exhibit any transcriptional activity. Molecular modeling suggests that V679A and R695H abrogate the auto-cleavage function of the ICA homo-trimer by destabilizing its homo-trimeric assembly. We also found that the ICA homo-trimer can tolerate one copy of Myrf-V679A or Myrf-R695H for its auto-cleavage function, indicating that V679A and R695H are not dominant negatives. Thus, if V679A and R695H in a heterozygous state caused birth defects, it would be via haploinsufficiency of MYRF.

A principled strategy for mapping enhancers to genes.

Mapping enhancers to genes is a fundamental goal of modern biology. We have developed an innovative strategy that maps enhancers to genes in a principled manner. We illustrate its power by applying it to Myrf. Despite being a master regulator of oligodendrocytes, oligodendrocyte enhancers governing Myrf expression remain elusive. Since chromatin conformation capture studies have shown that a gene and its enhancer tend to be found in the same topologically associating domain (TAD), we started with the delineation of the Myrf TAD. A genome-wide map of putative oligodendrocyte enhancers uncovered 6 putative oligodendrocyte enhancers in the Myrf TAD, narrowing down the search space for Myrf enhancers from the entire genome to 6 loci in a principled manner. Epigenome editing experiments revealed that two of them govern Myrf expression for oligodendrocyte development. Our new method is simple, principled, and powerful, providing a systematic way to find enhancers that regulate the expression of a gene of interest. Since it can be applied to most cell types, it would greatly facilitate our effort to unravel transcriptional regulatory networks of diverse cell types.

Are gestures worth a thousand words? Verbal and nonverbal communication during robot-assisted surgery.

Communication breakdowns in the operating room (OR) have been linked to errors during surgery. Robot-assisted surgery (RAS), a new surgical technology, can lead to new challenges in communication owing to the remote location of the surgeon away from the patient and bedside assistants. Nevertheless, few studies have studied communication strategies during RAS. In this study, 11 robot-assisted radical prostatectomies were recorded and the interaction events between the surgeon and two bedside surgical team members were categorized by modality (verbal/nonverbal), topic, and pair (sender and receiver). Both verbal and nonverbal modalities were used by all pairs. The percentage of nonverbal interactions differed significantly by pair: 66% for the Surgeon-Physician Assistant, 50% for the Physician Assistant-Scrub Nurse, and 25% for the Surgeon-Scrub Nurse, indicating different communication strategies across pairs. In addition, there was a significant dependence between topic and the percentages of verbal and nonverbal events for all pairs. Strategies to improve team communication during RAS should take into account the use of verbal and nonverbal communication means and the variation in interaction strategies based on the topic of communication.

Use of Robotic Anastomosis Competency Evaluation (RACE) for assessment of surgical competency during urethrovesical anastomosis.

INTRODUCTION: We sought to evaluate the Robotic Anastomosis Competency Evaluation (RACE), a validated tool that objectively quantifies surgical skills specifically for urethrovesical anastomosis (UVA), as a tool to track progress of trainees, and to determine the predictive value of RACE. METHODS: UVAs performed by trainees at our institution were evaluated using RACE over a period of two years. Trainees were supervised by an experienced robotic surgeon. Outcomes included trainee-related variables (RACE score, proportion of UVA performed by trainee, and suturing speed), and clinical outcomes (total UVA duration, postoperative urinary continence, and UVA-related complications). Significance was determined using linear regression analysis. RESULTS: A total of 51 UVAs performed by six trainees were evaluated. Trainee RACE scores (19.8 to 22.3; p=0.01) and trainee proportion of UVA (67% to 80%; p=0.003) improved significantly over time. Trainee suture speed was significantly associated with RACE score (mean speed range 0.54-0.74 sutures/minute; p=0.03). Neither urinary continence at six weeks nor six months was significantly associated with RACE score (p=0.17 and p=0.15, respectively), and only one UVA-related postoperative complication was reported. CONCLUSIONS: Trainee RACE scores improved and proportion of UVA performed by trainees increased over time. RACE can be used as an objective measure of surgical performance during training. Strict mentor supervision allowed safe training without compromising patient outcomes.

Elucidating the transactivation domain of the pleiotropic transcription factor Myrf.

Myrf is a newly discovered membrane-bound transcription factor that plays an essential role in as diverse organisms as human, worm, and slime mold. Myrf is generated as a type-II membrane protein in the endoplasmic reticulum (ER). It forms homo-oligomers to undergo auto-cleavage that releases Myrf N-terminal fragment from the ER membrane as a homo-trimer. The homo-trimer of Myrf N-terminal fragments enters the nucleus and binds the Myrf motif to activate transcription. Despite its prominent role as a transcriptional activator, little is known about the transactivation domain of Myrf. Here, we report that the N-terminal-most (NTM) domain of Myrf is required for transcriptional activity and, when fused to a Gal4 fragment, enables it to activate transcription. The transactivation function of the NTM domain did not require homo-trimerization. We also discovered that the NTM domain can be sumoylated at three lysine residues (K123, K208, and K276), with K276 serving as the main acceptor. K276 sumoylation repressed the transactivation function of the NTM domain without affecting the stability or nuclear localization of Myrf N-terminal fragment. In sum, this study identifies the NTM domain as the transactivation domain of Myrf and the potential regulatory impact of its K276 sumoylation.

Resveratrol and Pterostilbene Exhibit Anticancer Properties Involving the Downregulation of HPV Oncoprotein E6 in Cervical Cancer Cells.

Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents in targeting cervical cancer cells, having low IC50 values in the µM range. They decrease clonogenic survival, reduce cell migration, arrest cells at the S-phase, and reduce the number of mitotic cells. These findings were significant, with pterostilbene often being more effective than resveratrol. Resveratrol and to a greater extent pterostilbene downregulates the HPV oncoprotein E6, induces caspase-3 activation, and upregulates p53 protein levels. Results point to a mechanism that may involve the downregulation of the HPV E6 oncoprotein, activation of apoptotic pathways, and re-establishment of functional p53 protein, with pterostilbene showing greater efficacy than resveratrol.

Homo-trimerization is essential for the transcription factor function of Myrf for oligodendrocyte differentiation.

Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance.

The Loud Surgeon Behind the Console: Understanding Team Activities During Robot-Assisted Surgery.

OBJECTIVES: To design a data collection methodology to capture team activities during robot-assisted surgery (RAS) (team communications, surgical flow, and procedural interruptions), and use relevant disciplines of Industrial Engineering and Human Factors Engineering to uncover key issues impeding surgical flow and guide evidence-based strategic changes to enhance surgical performance and improve outcomes. DESIGN: Field study, to determine the feasibility of the proposed methodology. SETTING: Recording the operating room (OR) environment during robot-assisted surgeries (RAS). The data collection system included recordings from the console and 3 aerial cameras, in addition to 8 lapel microphones (1 for each OR team member). Questionnaires on team familiarity and cognitive load were collected. PARTICIPANTS: In all, 37 patients and 89 OR staff members have consented to participate in the study. RESULTS: Overall, 37 RAS procedures were recorded (130 console hours). A pilot procedure was evaluated in detail. We were able to characterize team communications in terms of flow, mode, topic, and form. Surgical flow was evaluated in terms of duration, location, personnel involved, purpose, and if movements were avoidable or not. Procedural interruptions were characterized according to their duration, cause, mode of communication, and personnel involved. CONCLUSION: This methodology allowed for the capture of a wide variety of team activities during RAS that would serve as a solid platform to improve nontechnical aspects of RAS.

Technical mentorship during robot-assisted surgery: a cognitive analysis.

OBJECTIVE: To investigate cognitive and mental workload assessments, which may play a critical role in defining successful mentorship. MATERIALS AND METHODS: The 'Mind Maps' project aimed at evaluating cognitive function with regard to surgeon's expertise and trainee's skills. The study included electroencephalogram (EEG) recordings of a mentor observing trainee surgeons in 20 procedures involving extended lymph node dissection (eLND) or urethrovesical anastomosis (UVA), with simultaneous assessment of trainees using the National Aeronautics and Space Administration Task Load index (NASA-TLX) questionnaire. We also compared the brain activity of the mentor during this study with his own brain activity while actually performing the same surgical steps from previous procedures populated in the 'Mind Maps' project. RESULTS: During eLND and UVA, when the mentor thought the trainee's mental demand and effort were low based on his NASA-TLX questionnaire (not satisfied with his performance), his EEG-based mental workload increased (reflecting more concern and attention). The mentor was mentally engaged and concerned while he was engrossed in observing the surgery. This was further supported by the finding that there was no significant difference in the mental demands and workload between observing and operating for the expert surgeon. CONCLUSIONS: This study objectively evaluated the cognitive engagement of a surgical mentor teaching technical skills during surgery. The study provides a deeper understanding of how surgical teaching actually works and opens new horizons for assessment and teaching of surgery. Further research is needed to study the feasibility of this novel concept in assessment and guidance of surgical performance.

Ambulatory movements, team dynamics and interactions during robot-assisted surgery.

OBJECTIVE: To analyse ambulatory movements and team dynamics during robot-assisted surgery (RAS), and to investigate whether congestion of the physical space associated with robotic technology led to workflow challenges or predisposed to errors and adverse events. METHODS: With institutional review board approval, we retrospectively reviewed 10 recorded robot-assisted radical prostatectomies in a single operating room (OR). The OR was divided into eight zones, and all movements were tracked and described in terms of start and end zones, duration, personnel and purpose. Movements were further classified into avoidable (can be eliminated/improved) and unavoidable (necessary for completion of the procedure). RESULTS: The mean operating time was 166 min, of which ambulation constituted 27 min (16%). A total of 2 896 ambulatory movements were identified (mean: 290 ambulatory movements/procedure). Most of the movements were procedure-related (31%), and were performed by the circulating nurse. We identified 11 main pathways in the OR; the heaviest traffic was between the circulating nurse zone, transit zone and supply-1 zone. A total of 50% of ambulatory movements were found to be avoidable. CONCLUSION: More than half of the movements during RAS can be eliminated with an improved OR setting. More studies are needed to design an evidence-based OR layout that enhances access, workflow and patient safety.

Understanding Cognitive Performance During Robot-Assisted Surgery.

OBJECTIVE: To understand cognitive function of an expert surgeon in various surgical scenarios while performing robot-assisted surgery. MATERIALS AND METHODS: In an Internal Review Board approved study, National Aeronautics and Space Administration-Task Load Index (NASA-TLX) questionnaire with surgical field notes were simultaneously completed. A wireless electroencephalography (EEG) headset was used to monitor brain activity during all procedures. Three key portions were evaluated: lysis of adhesions, extended lymph node dissection, and urethro-vesical anastomosis (UVA). Cognitive metrics extracted were distraction, mental workload, and mental state. RESULTS: In evaluating lysis of adhesions, mental state (EEG) was associated with better performance (NASA-TLX). Utilizing more mental resources resulted in better performance as self-reported. Outcomes of lysis were highly dependent on cognitive function and decision-making skills. In evaluating extended lymph node dissection, there was a negative correlation between distraction level (EEG) and mental demand, physical demand and effort (NASA-TLX). Similar to lysis of adhesion, utilizing more mental resources resulted in better performance (NASA-TLX). Lastly, with UVA, workload (EEG) negatively correlated with mental and temporal demand and was associated with better performance (NASA-TLX). The EEG recorded workload as seen here was a combination of both cognitive performance (finding solution) and motor workload (execution). Majority of workload was contributed by motor workload of an expert surgeon. During UVA, muscle memory and motor skills of expert are keys to completing the UVA. CONCLUSION: Cognitive analysis shows that expert surgeons utilized different mental resources based on their need.

Crystal structure of seleno-l-cystine di-hydro-chloride.

Numerous crystal structures are available for the dimeric amino acid cystine. In proteins it is formed by oxidation of the -SH thiol groups of two closely spaced cysteine residues, resulting in the formation of a familiar di-sulfide bridge. The title compound [systematic name: (R,R)-1,1'-dicarb-oxy-2,2'-(diselanedi-yl)diethanaminium dichloride], C6H14N2O4Se2 (2+)·2Cl(-), is the first example of a small mol-ecule structure of the biologically important analogue with a -CH2-Se-Se-CH2- bridging unit. Bond lengths and angles of seleno-l-cystine di-hydro-chloride and its isotypic sulfur analogue l-cystine di-hydro-chloride are compared.