MorphoSim: an efficient and scalable phase-field framework for accurately simulating multicellular morphologies.

The phase field model can accurately simulate the evolution of microstructures with complex morphologies, and it has been widely used for cell modeling in the last two decades. However, compared to other cellular models such as the coarse-grained model and the vertex model, its high computational cost caused by three-dimensional spatial discretization hampered its application and scalability, especially for multicellular organisms. Recently, we built a phase field model coupled with in vivo imaging data to accurately reconstruct the embryonic morphogenesis of Caenorhabditis elegans from 1- to 8-cell stages. In this work, we propose an improved phase field model by using the stabilized numerical scheme and modified volume constriction. Then we present a scalable phase-field framework, MorphoSim, which is 100 times more efficient than the previous one and can simulate over 100 mechanically interacting cells. Finally, we demonstrate how MorphoSim can be successfully applied to reproduce the assembly, self-repairing, and dissociation of a synthetic artificial multicellular system - the synNotch system.

Computable early Caenorhabditis elegans embryo with a phase field model.

Morphogenesis is a precise and robust dynamic process during metazoan embryogenesis, consisting of both cell proliferation and cell migration. Despite the fact that much is known about specific regulations at molecular level, how cell proliferation and migration together drive the morphogenesis at cellular and organismic levels is not well understood. Using Caenorhabditis elegans as the model animal, we present a phase field model to compute early embryonic morphogenesis within a confined eggshell. With physical information about cell division obtained from three-dimensional time-lapse cellular imaging experiments, the model can precisely reproduce the early morphogenesis process as seen in vivo, including time evolution of location and morphology of each cell. Furthermore, the model can be used to reveal key cell-cell attractions critical to the development of C. elegans embryo. Our work demonstrates how genetic programming and physical forces collaborate to drive morphogenesis and provides a predictive model to decipher the underlying mechanism.

Tuning Cell Motility via Cell Tension with a Mechanochemical Cell Migration Model.

Cell migration is orchestrated by a complicated mechanochemical system. However, few cell migration models take into account the coupling between the biochemical network and mechanical factors. Here, we construct a mechanochemical cell migration model to study the cell tension effect on cell migration. Our model incorporates the interactions between Rac-GTP, Rac-GDP, F-actin, myosin, and cell tension, and it is very convenient in capturing the change of cell shape by taking the phase field approach. This model captures the characteristic features of cell polarization, cell shape change, and cell migration modes. It shows that cell tension inhibits migration ability monotonically when cells are applied with persistent external stimuli. On the other hand, if random internal noise is significant, the regulation of cell tension exerts a nonmonotonic effect on cell migration. Because the increase of cell tension hinders the formation of multiple protrusions, migration ability could be maximized at intermediate cell tension under random internal noise. These model predictions are consistent with our single-cell experiments and other experimental results.

Carotid endarterectomy for asymptomatic carotid stenosis is safe in octogenarians.

OBJECTIVE: Carotid endarterectomy (CEA) is the gold standard to prevent a recurrent stroke in symptomatic patients with carotid stenosis. However, in the modern era, the benefit of CEA in asymptomatic octogenarian patients has come into question. This study investigates real-world outcomes of CEA in asymptomatic octogenarians. METHODS: Patients who underwent CEA for asymptomatic carotid stenosis were identified in the American College of Surgeons National Surgical Quality Improvement Program CEA-targeted database from 2012 to 2017. They were stratified into two groups: octogenarians (≥80 years old) and younger patients (<80 years old). The 30-day outcomes evaluated included mortality and major morbidities such as stroke, cardiac events, pulmonary, and renal dysfunction. Multivariable logistic regression was used for data analysis. RESULTS: We identified 13,846 patients with asymptomatic carotid stenosis who underwent an elective CEA including 2509 octogenarians and 11,337 younger patients. Octogenarians were more likely to be female and less likely to be diabetic or smokers compared with younger patients. There was no difference in preoperative use of statins or antiplatelet therapy. Examination of 30-day outcomes revealed that octogenarians had slightly higher mortality (1.2% vs 0.5%; odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P < .01), and a higher risk of return to the operating room (3.3% vs 2.3%; odds ratio, 1.4; 95% confidence interval, 1.1-1.9; P = .01). However, there was no difference between octogenarians and younger patients in adverse cardiac events or pulmonary, renal, or wound complications. Twenty-five octogenarian and 138 younger patients suffered from periprocedural stroke at a similar rate (1.0% vs 1.2%; P = .54). Stroke/death occurred for 51 of 2509 patients (2.0%) in the older group and 184 of 11,337 patients (1.6%) in the younger group, a difference that was not significant (P = .15). CONCLUSIONS: The 30-day outcomes of CEA in octogenarians are comparable with those in younger patients. Although the octogenarians had slightly higher mortality than younger patients, the absolute risk of mortality was still low at 1.2%. Therefore, CEA is safe in asymptomatic carotid stenosis in octogenarians. Overall life expectancy and preoperative functional status, rather than age, should be the major determinants in the decision to operate.

Rongchang and Xifeng capsules suppress pentylenetetrazole-induced seizures and change rest/wake behavior in zebrafish larvae.

OBJECTIVE: To evaluate the effects of Rongchang capsule and Xifeng capsule on pentylenetetrazole- induced epilepsy in zebrafish larvae and to explore the possible mechanisms behind their actions. METHODS: We utilized a trajectory tracking system to monitor seizures in zebrafish larva to confirm that certain concentrations of Rongchang capsule and Xifeng capsule produce antiepileptic effects. c-fos expression was assessed by quantitative reverse transcription-polymerase chain reaction to validate the efficacy of the capsules. Rest/wake behavior and correlation analysis predicted the targets of Rongchang capsule and Xifeng capsule. RESULTS: Larval movement times and total distances traveled by zebrafish larvae experiencing pentylenetetrazole (PTZ)-induced seizures were decreased by valproate treatment. Rongchang (500 µg/mL) and Xifeng (200 µg/mL) rescued the epileptic behaviors and down-regulated c-fos expression in the brains of larvae, which indicated antiepileptic effects. The rest/wake behavioral profiles showed that Rongchang and Xifeng differentially decreased rest time at night and increased larval locomotor activities during the day. Based on correlation between the actions of the two capsules and known compounds, we predicted that they might change rest/wake behaviors by affecting serotonin, GABAergic and histamine signaling pathways. CONCLUSION: The efficacy of Rongchang capsule and Xifeng capsule in alleviating epilepsy-like behaviors and molecular responses was confirmed. Our study provides insight into the capsules' effect on epilepsy.

Robotic Right Colectomy for Colon Cancer: Comparison of Outcomes from a Single Institution with the ACS-NSQIP Database.

BACKGROUND: Robotic surgery has increased in recent years for the treatment of colorectal cancer; however, it is not yet the standard of care. This study aims to compare the 30-day outcomes after robotic colectomy for right-sided colon cancer from our institution with those from a national dataset, the targeted colectomy American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS: Patients undergoing elective, robotic, right colon resection for stage I, II, and III colon cancer were identified within the targeted colectomy ACS-NSQIP database from 2012 to 2014. Patients meeting the same criteria were identified within a prospectively maintained institutional database from 2009 to 2015. Univariate analyses using chi-square tests and Student's t-tests were done where appropriate to compare baseline characteristics and outcomes between the two groups. RESULTS: Patients at our institution had a significantly higher average number of lymph nodes retrieved (24.4 versus 20.1, P = .046). There was no statistically significant difference between the two groups regarding the incidence of wound infections, anastomotic leaks, blood transfusions, unplanned return to the operating room, or prolonged length of hospital stay. There were no 30-day mortalities at our institution and only one in the ACS-NSQIP database. CONCLUSIONS: Our institutional experience with robotic right colon resection is equivalent to that of a national sample. This study demonstrates the safety of performing robotic right hemicolectomy for the treatment of colon cancer.

Right Colon Resection for Colon Cancer: Does Surgical Approach Matter?

BACKGROUND: Surgical resection with curative intent remains the standard of care for colon cancer. This study aims to compare the 30-day outcomes and oncologic results following open, laparoscopic, and robot-assisted right colon resection for colon cancer using the Targeted Colectomy American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. MATERIALS AND METHODS: All patients undergoing elective, right colon resection with primary anastomosis were identified within the targeted colectomy ACS-NSQIP database. Only patients with stage I, II, or III colon cancer were included. The association of surgical approach with oncologic results and 30-day morbidity and mortality outcomes was investigated using a variety of statistical tests. RESULTS: A total of 3518 patients met inclusion criteria; 1024 (29.1%) underwent open surgery (OS), 2405 (63.4%) underwent laparoscopic surgery, and 89 (2.5%) underwent robotic surgery. Patients undergoing OS were significantly more likely to have positive resection margins (P < .001). Patients undergoing OS were significantly more likely to experience prolonged intubation (P = .02), deep wound infections (P = .001), wound dehiscence (P = .005), deep venous thrombosis (P = .04), bleeding requiring a blood transfusion (P < .001), a prolonged postoperative ileus (P < .001), and longer length of hospital stay (P < .001), and were more likely to die (P = .02). CONCLUSION: The laparoscopic approach to colon resection for colon cancer has lower 30-day morbidity compared to OS. The robotic approach is equivalent to the laparoscopic approach, and its utilization may increase in the future.

Identifiable risk factors for thirty-day complications following arthroscopic rotator cuff repair.

OBJECTIVES: Shoulder arthroscopy has increased in frequency over the past decade, with rotator cuff repair comprising the majority of cases performed. Prior studies have detailed risk factors for 30-day complications and readmission rates after arthroscopic shoulder surgery using the National Surgical Quality Improvement Program (NSQIP) database, but no study has specifically looked at arthroscopic rotator cuff repair. The purpose of the study is to evaluate the risk factors for 30-day complications following arthroscopic rotator cuff repair using the NSQIP database. METHODS: The NSQIP database was queried for all patients undergoing arthroscopic rotator cuff repair from 2006-2015. Demographics and thirty-day outcomes for these patients were analyzed using univariate analyses and multivariate regression analysis to determine the risk factors for complications. RESULTS: 21,143 patients underwent arthroscopic rotator cuff repair, with 147 patients (0.70%) having a complication within 30-days. Univariate analysis found age >65 (p = 0.0028), male gender (p = 0.0053), elevated BMI (p = 0.0054), ASA class >2 (p < 0.0001), history of chronic obstructive pulmonary disease (p < 0.0001), hypertension (p < 0.0002), dyspnea (p < 0.0001), steroid use (p = 0.0350), and operative time >90 min (p = 0.0316) to be associated with increased risk of complications. Multivariate analysis found female sex to be protective or complication (OR 0.56, p = 0.0017), while American Society of Anesthesiology (ASA) class >2 (OR 1.51, p = 0.0335) and history of COPD (OR 2.41, p = 0.0030) and dyspnea (OR 1.89, p = 0.0359) to be risk factors for complication. The most common complication is venothromboembolic events, accounting for 36.7% of all complications. CONCLUSION: Male sex, ASA class > 2, and history of COPD and dyspnea were independent risk factors for thirty-day complications following arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: IV.

Patient Awareness of Local Drug Price Variation and the Factors That Influence Pharmacy Choice: A Cross-sectional Survey Study

BACKGROUND: High out-of-pocket drug expenditures are increasingly common in dermatology. Patients may not be aware that prices vary among pharmacies and consequently may not shop for the lowest cost. OBJECTIVE: To determine what factors influence pharmacy choice and the effect of providing local prescription prices on pharmacy selection. We hypothesized that patients do not "shop around" due to lack of knowledge of price variation and would choose a pharmacy based on costs if educated on price disparity. METHODS: Between July and August 2016, we administered a cross-sectional anonymous survey to adults visiting four outpatient clinics at an academic tertiary care center in Washington, D.C. Participants answered questions before and after viewing a list of prescription drug prices from local pharmacies. RESULTS: 287 surveys were administered to a convenience sample of adults (age ≥ 18 and literate in English). Of the 287 participants, 218 fully completed the survey; 55.1% were women and 40.5% were over age 40. When considering a cost savings of $10-25, 65% would switch pharmacies if the distance were the same, and 21.3% would switch if the distance were 45-minutes further. After price education, fewer participants felt that drug price knowledge would ultimately influence pharmacy choice (P less than 0.0001). However, respondents' intended frequency of researching price online, calling a pharmacy to ask about price, and comparing price between pharmacies before filling a prescription all increased, compared to prior self-reported frequencies (P less than 0.001). Specifically, participants with $75,000-$99,999 income were more likely to compare prices than those with income below $45,000 (odds ratio [OR], 4.62; 95% confidence interval [CI], 1.24-17.28). CONCLUSION: In this study, pharmacy choice was more influenced by convenience than cost prior to drug price education. However, price education ultimately impacted intent to research prescription drug prices before selecting a pharmacy. Thus, knowledge of drug pricing may be useful in creating cost savings for patients.

Comparing hospital outcomes between open and closed tibia fractures treated with intramedullary fixation.

INTRODUCTION: Tibial shaft fractures comprise a large portion of operatively treated long bone fractures, and present with the highest rate of open injuries. Intramedullary fixation has become the standard of care for both open and closed injuries. The rates of short term complications and hospital length of stay for open and closed fractures treated with intramedullary fixation is not fully known. Previous series on tibia fractures were performed at high volume centers, and data were not generalizable, further they did not report on length of stay and the impact of preoperative variables on infections, complications and reoperation. We used a large surgical database to compare these outcomes while adjusting for preoperative risk factors. METHODS: Data were extracted from the ACS-NSQIP database from 2005 to 2014. Cases were identified based on CPT codes for intramedullary fixation and categorized as closed vs open based on ICD9 code. In addition to demographic and case data, primary analysis examined correlation between open and closed fracture status with infection, complications, reoperation and hospital length of stay. Secondary analysis examined preoperative variables including gender, race, age, BMI, and diabetes effect on outcomes. RESULTS: There were 272 cases identified. There were no significant demographic differences between open and closed tibia fracture cases. Open fracture status did not increase the rate of infection, 30day complications, reoperation, or length of stay. The only preoperative factor that correlated with length of stay was age. There was no correlation between BMI, presence of insulin dependent and nondependent diabetes, and any outcome measure. DISCUSSION: When considering the complication rates for open and closed tibial shaft fractures treated with intramedullary fixation, there is no difference between 30-day complication rate, length of stay, or return to the operating room. Our reported postoperative infection rates were comparable to previous series, adding validity to our results. The heterogeneity of the hospitals included in ACS-NSQIP database allow our data to be generalizable. These methods may underrepresent the true occurrence of infection as operatively treated tibia infections may present late, requiring late revision. Despite limitations, the data reflect on the current burden of managing these once devastating injuries.

Biological impacts of glyphosate on morphology, embryo biomechanics and larval behavior in zebrafish (Danio rerio).

All of these days, residues of herbicides such as glyphosate are widely distributed in the environment. The ubiquitous use of glyphosate has drawn extensive attention to its toxicity as an organic pollutant. In this study, we employed larval zebrafish as an animal model to evaluate the effect of different concentrations of glyphosate on early development via morphological, biomechanics, behavioral and physiological analyses. Morphological results showed that an obvious delay occurred in the epiboly process and body length, eye and head area were reduced at concentrations higher than 10 mg/L. The expression of ntl (no tail) shortened and krox20 (also known as Egr2b, early growth response 2b) changed as the glyphosate concentration increased, but there was no change in the expression of shh (sonic hedgehog). In addition, biomechanical analysis of the elasticity of chorion indicated that treated embryos' surface tension was declined. Furthermore, a 48-h locomotion test revealed that embryonic exposure to glyphosate significantly elevated locomotor activities, which is probably attributed to motoneuronal damage. The decreased surface tension of chorion and the increased locomotive activities may contribute to the hatching rates after glyphosate treatment. Our study enriches the researches of evaluating glyphosate toxicity and probablely plays a warning role in herbicides used in farming.

Analysis of fall injuries by body mass index.

OBJECTIVE: To examine the association of body mass index (BMI) and fall injuries. METHODS: Data were derived from the 2010 Behavioral Risk Factor Surveillance System and included subjects aged 45 years and older from Texas. The outcome was self-reported falls that resulted in injury to the respondents. Analysis of fall injuries by BMI was conducted and standard errors, 95% confidence intervals (CIs), and coefficients of variation were reported. Complex sample multivariate Poisson regression was used to examine the association of BMI and fall injuries. RESULTS: A total of 18,077 subjects were surveyed in 2010, and 13,235 subjects were aged 45 years old and older. The mean BMI was higher (29.94 vs 28.32 kg/m(2)) among those who reported fall injuries compared with those who did not. The fall injuries reported by obese respondents (relative risk [RR] 1.67) were found to be significantly (P = 0.031) higher compared with normal-weight respondents in the multivariate regression. Other risk factors that had significant association with fall injuries (when adjusted for BMI) were activity limitations (RR 5.00, 95% CI 3.36-7.46) compared with no limitations, and not having formal employment (homemaker: RR 2.68, 95% CI 1.33-5.37; unable to work: RR 5.01, 95% CI 1.87-13.29; out of work and students: RR 3.21, 95% CI 1.41-7.29) compared with the employed population. CONCLUSIONS: There is a significant association between obesity and fall injuries in adults aged 45 years old and older in Texas. Interventions in fall prevention, although generally targeted at present to older adults, also should take into account the weight status of the subjects.