Progenitor division and cell autonomous neurosecretion are required for rod photoreceptor sublaminar positioning.

Migration is essential for the laminar stratification and connectivity of neurons in the central nervous system. In the retina, photoreceptors (PRs) migrate to positions according to birthdate, with early-born cells localizing to the basal-most side of the outer nuclear layer. It was proposed that apical progenitor mitoses physically drive these basal translocations non-cell autonomously, but direct evidence is lacking, and whether other mechanisms participate is unknown. Here, combining loss- or gain-of-function assays to manipulate cell cycle regulators (Sonic hedgehog, Cdkn1a/p21) with an in vivo lentiviral labelling strategy, we demonstrate that progenitor division is one of two forces driving basal translocation of rod soma. Indeed, replacing Shh activity rescues abnormal rod translocation in retinal explants. Unexpectedly, we show that rod differentiation also promotes rod soma translocation. While outer segment function or formation is dispensable, Crx and SNARE-dependent synaptic function are essential. Thus, both non-cell and cell autonomous mechanisms underpin PR soma sublaminar positioning in the mammalian retina.

Photoreceptor nanotubes mediate the in vivo exchange of intracellular material.

Emerging evidence suggests that intracellular molecules and organelles transfer between cells during embryonic development, tissue homeostasis and disease. We and others recently showed that transplanted and host photoreceptors engage in bidirectional transfer of intracellular material in the recipient retina, a process termed material transfer (MT). We used cell transplantation, advanced tissue imaging approaches, genetic and pharmacologic interventions and primary cell culture to characterize and elucidate the mechanism of MT. We show that MT correlates with donor cell persistence and the accumulation of donor-derived proteins, mitochondria and transcripts in acceptor cells in vivo. MT requires cell contact in vitro and is associated with the formation of stable microtubule-containing protrusions, termed photoreceptor nanotubes (Ph NTs), that connect donor and host cells in vivo and in vitro. Ph NTs mediate GFP transfer between connected cells in vitro. Furthermore, interfering with Ph NT outgrowth by targeting Rho GTPase-dependent actin remodelling inhibits MT in vivo. Collectively, our observations provide evidence for horizontal exchange of intracellular material via nanotube-like connections between neurons in vivo.

HepG2 PMM2-CDG knockout model: A versatile platform for variant and therapeutic evaluation.

Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent congenital disorder of glycosylation, is an autosomal recessive disease caused by biallelic pathogenic variants in the PMM2 gene. There is no cure for this multisystemic syndrome. Some of the therapeutic approaches that are currently in development include mannose-1-phosphate replacement therapy, drug repurposing, and the use of small chemical molecules to correct folding defects. Preclinical models are needed to evaluate the efficacy of treatments to overcome the high lethality of the available animal model. In addition, the number of variants with unknown significance is increasing in clinical settings. This study presents the generation of a cellular disease model by knocking out the PMM2 gene in the hepatoma HepG2 cell line using CRISPR-Cas9 gene editing. The HepG2 knockout model accurately replicates the PMM2-CDG phenotype, exhibiting a complete absence of PMM2 protein and mRNA, a 90% decrease in PMM enzymatic activity, and altered ICAM-1, LAMP1 and A1AT glycoprotein patterns. The evaluation of PMM2 disease-causing variants validates the model's utility for studying new PMM2 clinical variants, providing insights for diagnosis and potentially for evaluating therapies. A CRISPR-Cas9-generated HepG2 knockout model accurately recapitulates the PMM2-CDG phenotype, providing a valuable tool for assessing disease-causing variants and advancing therapeutic strategies.

Small-Molecule-Directed Endogenous Regeneration of Visual Function in a Mammalian Retinal Degeneration Model.

Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems. When tested in a disease-relevant murine model of adult retinal degeneration (MNU-induced retinal degeneration), we observed that four repeat intravitreal injections of the compound improved the thickness of the outer nuclear layer along with the regeneration of the visual function, as measured with ERG, visual acuity, and contrast sensitivity tests. This serves as a proof of concept for the use of a small molecule to promote endogenous regeneration in the eye.

Designing nutrition-sensitive agriculture (NSA) interventions with multi-criteria decision analysis (MCDA): a review.

Despite the efforts to end malnutrition through intensive agriculture of caloric crops, micronutrient deficiencies and other forms of malnutrition persist in vulnerable communities worldwide. Nutrition-sensitive agriculture (NSA) interventions are recognized as chances to address the causes of malnutrition. In this work, the different types of NSA interventions were explored, as well as the pathways through which they can improve nutrition (e.g., increasing biofortified crops and income generation via agricultural sales for a positive impact on access to nutritious foods, and simultaneously involving nutrition education to improve care practices and eventually nutritional status). Some NSA interventions focus on one pathway. Well-designed interventions, however, should follow multi-pathway approaches targeting the underlying causes of undernutrition within the selected population. The circumstances in which certain indicators should be used to measure the impact of an NSA intervention in each stage of the full pathway were also explained, as well as the need of enhancing the design of such interventions. Multi-criteria decision analysis (MCDA) has been employed to solve agriculture-related issues, but it has not been used to identify the optimal types of NSA interventions, metrics, and indicators based on the context of the community, priorities and objectives of the project managers and designers, etc.

Objective psychomotor laparoscopic skills evaluation using a low-cost wearable device based on accelerometry: construct and concurrent validity study.

BACKGROUND: Motion analysis of surgical maneuvers provides useful quantitative information for the objective evaluation of the surgeons. However, surgical simulation laboratories for laparoscopic training do not usually integrate devices that help quantify the level of skills of the surgeons due to their limited resources and the high costs of new technologies. The purpose of this study is to present the construct and concurrent validity of a low-cost motion tracking system, based on a wireless triaxial accelerometer, employed to objectively evaluate psychomotor skills of surgeons during laparoscopic training. METHODS: An accelerometry system, a wireless three-axis accelerometer with appearance of wristwatch, was placed on the dominant hand of the surgeons to register the motion during the laparoscopy practice with the EndoViS simulator, which simultaneously recorded the motion of the laparoscopic needle driver. This study included the participation of 30 surgeons (6 experts, 14 intermediates and 10 novices) who performed the task of intracorporeal knot-tying suture. Using 11 motion analysis parameters (MAPs), the performance of each participant was assessed. Subsequently, the scores of the three groups of surgeons were statistically analyzed. In addition, a validity study was conducted comparing the metrics between the accelerometry-tracking system and the EndoViS hybrid simulator. RESULTS: Construct validity was achieved for 8 of the 11 metrics examined with the accelerometry system. Concurrent validity demonstrated that there is a strong correlation between the results of the accelerometry system and the EndoViS simulator in 9 of 11 parameters, showing reliability of the accelerometry system as an objective evaluation method. CONCLUSION: The accelerometry system was successfully validated. This method is potentially useful to complement the objective evaluation of surgeons during laparoscopic practice in training environments such as box-trainers and simulators.

Face, content, and construct validity of the virtual immersive operating room simulator for training laparoscopic procedures.

BACKGROUND: The aim of this work is to present the face, content, and construct validation of the virtual immersive operating room simulator (VIORS) for procedural training of surgeons' laparoscopic psychomotor skills and evaluate the immersive training experience. METHODS: The VIORS simulator consists of an HMD Oculus Rift 2016 with a visor on a 1080 × 1200 pixel OLED screen, two positioning sensors with two adapted controls to simulate laparoscopic instruments, and an acrylic base to simulate the conventional laparoscopic setup. The immersion consists of a 360° virtual operating room environment, based on the EndoSuite at Hospital Infantil de Mexico Federico Gomez, which reproduces a configuration of equipment, instruments, and common distractions in the operating room during a laparoscopic cholecystectomy procedure. Forty-five surgeons, residents, and medicine students participated in this study: 27 novices, 13 intermediates, and 5 experts. They completed a questionnaire on the realism and operating room immersion, as well as their capabilities for laparoscopic procedural training, scored in the 5-point Likert scale. The data of instrument movement were recorded and analyzed using 13 movement analysis parameters (MAPs). The experience during training with VIORS was evaluated through NASA-TLX. RESULTS: The participants were enthusiastic about the immersion and sensation levels of the VIORS simulator, with positive scores on the realism and its capabilities for procedural training using VIORS. The results proved that the VIORS simulator was able to differentiate between surgeons with different skill levels. Statistically significant differences were found in nine MAPs, demonstrating their construct validity for the objective assessment of the procedural laparoscopic performance. At cognitive level, the inversion experience proves a moderate mental workload when the laparoscopic procedure is carried out. CONCLUSION: The VIORS simulator has been successfully presented and validated. The VIORS simulator is a useful and effective device for the training of procedural laparoscopic psychomotor skills.

HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.

HERC2 gene encodes an E3 ubiquitin ligase involved in several cellular processes by regulating the ubiquitylation of different protein substrates. Biallelic pathogenic sequence variants in the HERC2 gene are associated with HERC2 Angelman-like syndrome. In pathogenic HERC2 variants, complete absence or marked reduction in HERC2 protein levels are observed. The most common pathological variant, c.1781C > T (p.Pro594Leu), encodes an unstable HERC2 protein. A better understanding of how pathologic HERC2 variants affect intracellular signalling may aid definition of potential new therapies for these disorders. For this purpose, we studied patient-derived cells with the HERC2 Pro594Leu variant. We observed alteration of mitogen-activated protein kinase signalling pathways, reflected by increased levels of C-RAF protein and p38 phosphorylation. HERC2 knockdown experiments reproduced the same effects in other human and mouse cells. Moreover, we demonstrated that HERC2 and RAF proteins form molecular complexes, pull-down and proteomic experiments showed that HERC2 regulates C-RAF ubiquitylation and we found out that the p38 activation due to HERC2 depletion occurs in a RAF/MKK3-dependent manner. The displayed cellular response was that patient-derived and other human cells with HERC2 deficiency showed higher resistance to oxidative stress with an increase in the master regulator of the antioxidant response NRF2 and its target genes. This resistance was independent of p53 and abolished by RAF or p38 inhibitors. Altogether, these findings identify the activation of C-RAF/MKK3/p38 signalling pathway in HERC2 Angelman-like syndrome and highlight the inhibition of RAF activity as a potential therapeutic option for individuals affected with these rare diseases.

Objective Evaluation of Laparoscopic Experience Based on Muscle Electromyography and Accelerometry Performing Circular Pattern Cutting Tasks: A Pilot Study.

Purpose.The aim of this work is to present a new physical laparoscopy simulator with an electromyography (EMG)/accelerometry-based muscle activity recording system, EvalLap EMG-ACC, and perform objective evaluation of laparoscopic skills based on the quantification of muscle activity of participants with different levels of laparoscopic experience. Methods. EMG and ACC signals were obtained from 14 participants (6 experts, 8 medical students) performing circular pattern cutting tasks using a laparoscopic box trainer with the Trigno (Delsys Inc, Natick, MA) portable wireless system of 16 wireless sensors. Sensors were placed on the proximal and distal muscles of the upper extremities. Seven evaluation metrics were proposed and compared between skilled and novice surgeons. Results. The proximal and distal arm muscles (trapezius, deltoids, biceps, and forearms) were most active while executing laparoscopic tasks. Laparoscopic experience was associated with differences in EMG amplitude (Aavg), muscle activity (iEMG), hand acceleration (iACH), user movement (iAC), and muscle fatigue. For the cutting task, the deltoid, bicep, forearm EMG amplitude, and user movement significantly differed between experience groups. Conclusion. This pilot study demonstrates that different muscle groups are preferentially activated during laparoscopic tasks depending on the level of surgical experience. Expert surgeons showed less muscle activity compared with novices. EvalLap EMG-ACC represents a promising means to distinguish surgeons with basic cutting skills from those who have not yet developed these skills.

Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.

Protein ubiquitylation acts as a complex cell signaling mechanism since the formation of different mono- and polyubiquitin chains determines the substrate's fate in the cell. E3 ligases define the specificity of this reaction by catalyzing the attachment of ubiquitin to the substrate protein. Thus, they represent an important regulatory component of this process. Large HERC ubiquitin ligases belong to the HECT E3 protein family and comprise HERC1 and HERC2 proteins. The physiological relevance of the Large HERCs is illustrated by their involvement in different pathologies, with a notable implication in cancer and neurological diseases. Understanding how cell signaling is altered in these different pathologies is important for uncovering novel therapeutic targets. To this end, this review summarizes the recent advances in how the Large HERCs regulate the MAPK signaling pathways. In addition, we emphasize the potential therapeutic strategies that could be followed to ameliorate the alterations in MAPK signaling caused by Large HERC deficiencies, focusing on the use of specific inhibitors and proteolysis-targeting chimeras.

Sweet potato flour (Ipomoea batatas) as natural antioxidant on carcass yield and meat physicochemical characteristics of Creole chickens of Mexico and Cobb 500.

Antioxidants are considered functional additives against oxidative stress since they avoid nutritional decline in the meat. The main objective of the present study is to evaluate the effect of sweet potato flour (SPF) as a natural antioxidant on carcass yield and physicochemical characteristics of Creole chickens of Mexico (CChM) and Cobb 500 broilers. In total, 210 chickens (105 CChM and 105 Cobb 500 chickens) were randomly assigned to three treatments: 0, 500, and 1000 mg of SPF kg-1 of feed. The Cobb 500 chickens showed higher carcass yield (hot and cold), breast, and breast fillet, whereas the CChM had higher thigh yield (P ≤ 0.05). The yield on the previously mentioned variables was not affected by the inclusion levels of SPF. The initial pH differed because of the effect of the chicken's genotype and the addition of SPF, which was higher on Cobb 500 chicken and on those that were not supplemented with SPF. The birds' skin that consumed SPF presented higher yellowness after 24 h (P ≤ 0.05). CChM manifested a higher dry matter and protein content and a lower content of ash and fat (P ≤ 0.05). In conclusion, Cobb 500 chickens present a higher carcass yield and its components, in addition to a less acid pH; however, CChM offer a higher nutritional contribution, whereas the 500 and 1000 mg addition of SPF increases the skin yellowness, which makes it an alterorganic as a pigment on broiler chicken production.

Growth performance, carcass, and meat quality traits of Tropical Milking criollo bulls fed with two energy-level diets.

The aim of this study was to determine the effect of two energy-level diets on the beef performance of Tropical Milking criollo bulls grouped by weight and age in three periods: initial, middle, and final. Evidence on intensive beef production from Tropical Milking criollo cattle breeds are unknown, and productive alternatives for dairy producers in the hot tropics are needed. Bulls were fed in each period with low (LE, 2.2 Mcal ME/kg DM) and high (HE, 2.9 Mcal ME/kg DM) energy diets and content phase feeding protein of 14.5, 12.0, and 10.3%, respectively. For each period, ten bulls were randomly assigned to diets. In all periods, growth performance for final body weight, average daily gain, feed intake, and feed conversion were all superior in HE (p ≤ 0.05). For the final period, slaughter body, hot and cold carcass weights, and dressing were also superior in HE (p ≤ 0.05); for meat quality traits, differences were observed in muscles Longissimus dorsi, Semimembranosus, Infraspinatus, and Serratus ventralis for pH and tenderness (p ≤ 0.05), although not for diets. For color L*, a*, and b* system, neither diet nor muscle had effect on L* (p > 0.05); however, the diet-muscle interaction was significant for a* (p ≤ 0.05), and only muscle effect was detected for b* (p ≤ 0.05). Tropical Milking bulls responded positively to a high-energy diet, despite not being a beef breed.

Diesel effects on some population attributes of Orthonychiurus folsomi Schäffer 1900 (Collembola: Onychiuridae) under laboratory conditions.

Soil contamination by hydrocarbons and its effects on population health and welfare is a growing concern, especially in urban environments with industrial activity. Indicator species complement the information obtained from the measurement of environment quality by using physicochemical variables. The objective of this study was to evaluate the response of a springtail species that could be potentially used as a bioindicator of hydrocarbon contaminated sites. We studied the effects of seven diesel concentrations on survival and other population parameters of Orthonychiurus folsomi under laboratory conditions; we evaluated the springtails response on survival, fecundity, population size, hatching and development time. Survival and fertility were analyzed by using generalized linear models (GLM). An ANOVA test was used to analyze the final population size and a Kruskal-Wallis test for oviposition, hatching, and development times. Results showed that diesel has negative effects on some population parameters. The most evident effects were recorded above 500 mg/kg concentrations. A significant decrease in survival, fertility, and population size was recorded in function of diesel concentration increase. The estimated LC50 for survival was 955 mg/kg. Oviposition and hatching time increased significantly when diesel concentrations were above 500 mg/kg, while development time increased slightly at low diesel concentrations but decreased at concentrations above 500 mg/kg. Population final size decreased as soil diesel concentrations increased. Due to the sensitive and rapid response of O. folsomi, it could be useful to detect diesel-contaminated soil, mainly in urban areas.

Volume Matters: Longitudinal Retrospective Cohort Study of Outcomes Following Consultation and Standardization of Adrenal Surgery.

PURPOSE: Subspecialization of adrenal surgery through regionalization has not been adequately evaluated. We assessed implementation of subspecialization and the association of regionalization with adrenalectomy outcomes in a community-based setting. METHODS: In this longitudinal retrospective cohort study, we used an interrupted time series analysis on consecutive adrenal surgeries at Kaiser Permanente Northern California, 2010-2019. The intervention was regionalization of surgery in 2016. Main outcomes include surgical volumes, operative time, length of stay, 30-day return-to-care, and 30-day complications obtained from the electronic medical record. t-Tests and multivariable models were used to analyze time trends in outcomes after accounting for changes in patient and disease characteristics. RESULTS: In total, 850 adrenal surgery cases were eligible. Between 2010 and 2019, the annual incidence of surgery (per 100,000 persons) increased from 2.4 (95% CI 1.9-3.1) to 4.1 (95% CI 3.5-4.8). Average annual surgeon volume increased from 2.4 (95% CI 1.6-3.1) to 9.9 (95% CI 4.9-14.9), while hospital volume increased from 3.5 (95% CI 2.3-4.6) to 15.4 (95% CI 6.9-24.0). Operative time was 34 (23-45) min faster in 2018-2019 compared with 2010-2011. After regionalization, same-day discharges increased to 64% in 2019 (p < 0.0001). The frequency of return-to-care (p = 0.69) and the overall complication rate (p = 0.31) did not change. CONCLUSIONS: Regionalizing adrenal surgery through surgical subspecialization and standardized care pathways was feasible and decreased operative time, and hospital stay, while increasing the frequency of same-day discharges without increasing return-to-care or complications.

Development of a 3D Motion Tracking System for the Analysis of Skills in Microsurgery.

Microsurgical skills of trainee surgeons have been subjectively evaluated due to the lack of technological tools. The objective of this investigation is to present the construct validity of the mitracks3D, which is a system designed to help in the objective evaluation of microsurgery trainees. To achieve this, a stereoscopic vision system records the 3D motion of two tweezers manipulated by surgeons during microsurgery training. Using motion analysis parameters (MAPs), quantitative information about their microsurgical skills and performance is obtained. For validation, 14 participants were enrolled and divided into two groups: expert microsurgeons (3 female, 2 male) and trainee surgeons (4 female, 5 male). The 3D motion tracking was acquired while the surgeons practiced with two training models: transferring objects and suture. Twelve MAPs were used to objective assessment the skill levels of each participant. Subsequent, statistical analysis was computed to compare the scores of both groups. Validation results showed statistically significant differences in 8 of the 12 MAPs and in 10 of the 12 MAPs using the transferring and the suturing models, respectively. The capability of mitracks3D to differentiate the performance of microsurgeons by analyzing their movements was shown. The mitracks3D system was successfully validated. With this system was possible to differentiate the psychomotor microsurgical skills between the two groups of surgeons. The mitracks3D system is a suitable device for the evaluation of microsurgical skills in a variety of surgical specialties that require it during the training of their residents.

Modeling of Photoreceptor Donor-Host Interaction Following Transplantation Reveals a Role for Crx, Müller Glia, and Rho/ROCK Signaling in Neurite Outgrowth.

The goal of photoreceptor transplantation is to establish functional synaptic connectivity between donor cells and second-order neurons in the host retina. There is, however, limited evidence of donor-host photoreceptor connectivity post-transplant. In this report, we investigated the effect of the host retinal environment on donor photoreceptor neurite outgrowth in vivo and identified a neurite outgrowth-promoting effect of host Crx(-/-) retinas following transplantation of purified photoreceptors expressing green fluorescent protein (GFP). To investigate the noncell autonomous factors that influence donor cell neurite outgrowth in vitro, we established a donor-host coculture system using postnatal retinal aggregates. Retinal cell aggregation is sensitive to several factors, including plate coating substrate, cell density, and the presence of Müller glia. Donor photoreceptors exhibit motility in aggregate cultures and can engraft into established aggregate structures. The neurite outgrowth-promoting phenotype observed in Crx(-/-) recipients in vivo is recapitulated in donor-host aggregate cocultures, demonstrating the utility of this surrogate in vitro approach. The removal of Müller glia from host aggregates reduced donor cell neurite outgrowth, identifying a role for this cell type in donor-host signaling. Although disruption of chondroitin sulfate proteoglycans in aggregates had no effect on the neurite outgrowth of donor photoreceptors, disruption of Rho/ROCK signaling enhanced outgrowth. Collectively, these data show a novel role of Crx, Müller glia, and Rho/ROCK signaling in controlling neurite outgrowth and provide an accessible in vitro model that can be used to screen for factors that regulate donor-host connectivity. Stem Cells 2019;37:529-541.

Construct validity of the SurgForce system for objective assessment of laparoscopic suturing skills.

BACKGROUND: Laparoscopic surgery requires a new set of skill to be learned by the surgeons, of which the most relevant is tissue manipulation. Excessive forces applied to the tissue can cause rupture during manipulation or ischemia when confronting both sides of the tissue. The aim of this study is to establish the construct validity of the SurgForce system for objective assessment of advanced laparoscopic skills, based on the force signal generated during suture tasks, and the development of force parameters for evaluating tissue handling interaction. METHODS: The SurgForce system, a tissue handling training device that measures dynamic force, was used to capture the force generated by surgeons with different levels of laparoscopic experience. For construct validity, 37 participants were enrolled in this study: 19 medical students, 12 residents of surgical specialties and 6 expert surgeons. All participants performed an intracorporeal knotting suture task over a synthetic tissue pad with a laparoscopic box-trainer. The force performance of the participants was analyzed using 11 force-based parameters with the application of the SurgForce system. Statistical analysis was performed between novice, intermediate, and expert groups using a Kruskal-Wallis test, and between the pairs of groups using a Mann-Whitney U-test. RESULTS: Overall, 9 of the 11 force-related parameters showed significant differences between the three study groups. Results between the pairs of groups presented significant differences in 5 force parameters proposed. Construct validity results demonstrated that the SurgForce system was able to differentiate force performance between surgeons with different levels of laparoscopic experience. CONCLUSION: The SurgForce system was successfully validated. This force system showed its potential to measure the force exerted on tissue for objective assessment of tissue handling skills in suturing tasks. Furthermore, its compact design allows the use of this device in conventional laparoscopic box-trainers.

Pigment Epithelium-Derived Factor (PEDF) Fragments Prevent Mouse Cone Photoreceptor Cell Loss Induced by Focal Phototoxicity In Vivo.

Here, we evaluated the effects of PEDF (pigment epithelium-derived factor) and PEDF peptides on cone-photoreceptor cell damage in a mouse model of focal LED-induced phototoxicity (LIP) in vivo. Swiss mice were dark-adapted overnight, anesthetized, and their left eyes were exposed to a blue LED placed over the cornea. Immediately after, intravitreal injection of PEDF, PEDF-peptide fragments 17-mer, 17-mer[H105A] or 17-mer[R99A] (all at 10 pmol) were administered into the left eye of each animal. BDNF (92 pmol) and bFGF (27 pmol) injections were positive controls, and vehicle negative control. After 7 days, LIP resulted in a consistent circular lesion located in the supratemporal quadrant and the number of S-cones were counted within an area centered on the lesion. Retinas treated with effectors had significantly greater S-cone numbers (PEDF (60%), 17-mer (56%), 17-mer [H105A] (57%), BDNF (64%) or bFGF (60%)) relative to their corresponding vehicle groups (≈42%). The 17-mer[R99A] with no PEDF receptor binding and no neurotrophic activity, PEDF combined with a molar excess of the PEDF receptor blocker P1 peptide, or with a PEDF-R enzymatic inhibitor had undetectable effects in S-cone survival. The findings demonstrated that the cone survival effects were mediated via interactions between the 17-mer region of the PEDF molecule and its PEDF-R receptor.

Design of a Dynamic Force Measurement System for Training and Evaluation of Suture Surgical Skills.

The aim of this study is to present the SurgeForce system, a tissue handling training device for analysis of dynamic force applied to the tissue and objective assessment of basic surgical skills during the suture process. The SurgeForce system consists of a mechanical base formed by two platforms joint with three stainless steel springs and a three axial digital accelerometer attached to the upper platform, which detects the dynamic force caused by a surgeon when performing a suture task over a synthetic tissue pad. Accelerometer data is sent to a control unit where preprocessing to transform the raw data into a force signal is done, and then, the force signal is sent to a computer application, which register the force exerted over the synthetic tissue pad. For validation, 17 participants (6 surgeons and 11 medical students) performed three simple interrupted sutures with knot tying using the SurgeForce system. Ten force-based metrics were proposed to evaluate their performance during the suturing task. Results of the validation showed statistical differences in 8 of 10 force-based parameters for assessment of basic surgical skills during the suture task. The SurgeForce system demonstrated its capacity to differentiate force-based performance of surgeons and medical students. The SurgeForce system has been successfully validated. This system was able to distinguish force performance between experts and novices, showing its potential to distinguish surgeons with basic suture skills from those who are not yet prepared.

Development and Preliminary Validation of a Rabbit Model of Duodenal Atresia for Training in Pediatric Surgical Skills.

Duodenal atresia is a congenital defect that requires advanced surgical skills. The objective of this study is to present an anatomical defect of duodenal atresia using a rabbit model and evaluate the preliminary experience for the training of surgical skills with pediatric surgeons. Adult white New Zealand male rabbits weighing 3.0 to 4.5 kg were used to create the defect. To simulate the bottom of the dilated blind pouch, the gastric antrum of the rabbit was obliterated using a 2-0 Prolene suture, and the cecal appendix was dissected to simulate the continuation of the duodenum. Participants performed laparoscopic duodenal atresia repair in this animal model using the iPhone trainer. Thirteen pediatric surgeons with experience in laparoscopic duodenal atresia repair assessed this model with a questionnaire on 5-point Likert-type scale. Overall, the simulated model of duodenal atresia obtained a general average score of 4.39. The highest observed average was for its physical realism, whereas the lowest score was in surgical experience. The global opinion of the model obtained a score of 4.40. In addition, all surgeons answered that this rabbit model showed the same complexity as newborns and young children in the repair of this type of defect. The inclusion of new models through rabbits in pediatric surgery programs will allow the development of advanced skills of pediatric residents and surgeons.