Topological defects of integer charge in cell monolayers.

Many cell types spontaneously order like nematic liquid crystals, and, as such, they form topological defects, which influence the cell organization. While defects with topological charge ±1/2 are common in cell monolayers, defects with charge ±1, which are thought to be relevant in the formation of protrusions in living systems, are more elusive. We use topographical patterns to impose topological charge of ±1 in controlled locations in cell monolayers. We study two types of cells, 3T6 fibroblasts and EpH-4 epithelial cells, and we compare their behavior on such patterns, characterizing the degree of alignment, the cell density near the defects, and their behavior at the defect core. We observe density variation in the 3T6 monolayers near both types of defects over the same length-scale. By choosing appropriate geometrical parameters of our topographical features, we identify a new behavior of 3T6 cells near the defects with topological charge +1, leading to a change in the cells' preferred shape. Our strategy allows a fine control of cell alignment near defects as a platform to study liquid crystalline properties of cells.

The Effects of Stiffness, Fluid Viscosity, and Geometry of Microenvironment in Homeostasis, Aging, and Diseases: A Brief Review.

Cells sense biophysical cues in the micro-environment and respond to the cues biochemically and biophysically. Proper responses from cells are critical to maintain the homeostasis in the body. Abnormal biophysical cues will cause pathological development in the cells; pathological or aging cells, on the other hand, can alter their micro-environment to become abnormal. In this minireview, we discuss four important biophysical cues of the micro-environment-stiffness, curvature, extracellular matrix (ECM) architecture and viscosity-in terms of their roles in health, aging, and diseases.

Umbilical hernias: the cost of waiting.

BACKGROUND: Umbilical hernias are well described in the literature, but its impact on health care is less understood. The purpose of this study was to investigate the effect of non-operative management of umbilical hernias on cost, work absenteeism, and resource utilization. METHODS: The Truven Health Database, consisting of 279 employers and over 3000 hospitals, was reviewed for all umbilical hernia patients, aged 18-64 who were enrolled in health plans for 12 months prior to surgery and 12 months after surgery. Patients were excluded if they had a recurrence or had been offered a "no surgery" approach within 1 year of the index date. The remaining patients were separated into surgery (open or laparoscopic repair) or no surgery (NS). Post-cost analysis at 90 and 365 days and estimated days off from work were reviewed for each group. RESULTS: The non-surgery cohort had a higher proportion of females and comorbidity index. Adjusted analysis showed significantly higher 90 and 365 costs for the surgery group (p < 0.0001), though the cost difference did decrease over time. NS group had significantly higher estimated days of health-care utilization at both the 90 (1.99 vs. 3.58 p < 0.0001) and 365 (8.69 vs. 11.04 p < 0.0001) day post-index mark. A subgroup analysis demonstrated laparoscopic repair had higher costs compared to open primarily due to higher index procedure costs (p < 0.05). CONCLUSIONS: Though the financial costs were found to be higher in the surgery group, the majority of these were due to the surgery itself. Significantly higher days of health-care utilization and estimated days off work were experienced in the NS group. It is our belief that early operative intervention will lead to decreased costs and resource utilization.

Prior treatment does not influence the performance or early outcome of per-oral endoscopic myotomy for achalasia.

INTRODUCTION: Per-oral endoscopic myotomy (POEM) is an emerging treatment for achalasia. Pneumatic dilation, botulinum toxin injection, and previous myotomy increase the difficulty of subsequent Heller myotomy, but their impact on POEM remains unknown. The purpose of this study was to compare patients who had undergone prior treatment for their achalasia to those undergoing POEM as an initial therapy. METHODS AND PROCEDURES: All patients undergoing POEM were entered into a prospective database from August 2012 to October 2014. Data collected included demographics, dysphagia and symptom survey scores, operative time, clips required for mucosotomy closure, perioperative complications and length of hospital stay. RESULTS: Forty-five patients underwent POEM during the study period. Fifteen (30%) had undergone previous treatment (seven Botox injection, five pneumatic dilation and three Heller myotomy). Primary POEM patients were younger than those who had had prior treatment (mean age 46 ± 17 vs. 64 ± 12 years, p < 0.001), but gender, body mass index and ASA class were not significantly different. There were no conversions to Heller myotomy or perioperative complications in either group. Operative time for primary POEM was 103 ± 27 versus 102 ± 29 min following prior treatment (p = 0.84). Mucosotomy closure required a median 7 (4-16) and 8 (5-16) clips, respectively (p = 0.08). Length of stay was 1 day in each group. Median dysphagia scores decreased from 4 (0-5) to 1 (0-4) following primary POEM and 4 (0-5) to 0 (0-4) in the prior treatment group (p = 0.45) during a median follow-up of 10 months (5-17 months). All patients in each group expressed satisfaction with their procedure and would undergo the procedure again given the benefit of hindsight. CONCLUSION: Per-oral endoscopic myotomy is a safe and effective treatment for achalasia which improves dysphagia and disease-specific quality of life. Previous endoscopic or laparoscopic treatment of achalasia does not affect the performance or early outcome of POEM.

Pulmonary immune changes early after laparoscopic antireflux surgery in lung transplant patients with gastroesophageal reflux disease.

BACKGROUND: The biologic mechanisms by which laparoscopic antireflux surgery (LARS) might influence the inflammatory process leading to bronchiolitis obliterans syndrome are unknown. We hypothesized that LARS alters the pulmonary immune profile in lung transplant patients with gastroesophageal reflux disease. METHODS: In 8 lung transplant patients with gastroesophageal reflux disease, we quantified and compared the pulmonary leukocyte differential and the concentration of inflammatory mediators in the bronchoalveolar lavage fluid (BALF) 4 weeks before LARS, 4 weeks after LARS, and 12 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome (graded 1-3 according to the International Society of Heart and Lung Transplantation guidelines), forced expiratory volume in 1 second trends, and survival were also examined. RESULTS: At 4 weeks after LARS, the percentages of neutrophils and lymphocytes in the BALF were reduced (from 6.6% to 2.8%, P = 0.049, and from 10.4% to 2.4%, P = 0.163, respectively). The percentage of macrophages increased (from 74.8% to 94.6%, P = 0.077). Finally, the BALF concentration of myeloperoxide and interleukin-1ß tended to decrease (from 2109 to 1033 U/mg, P = 0.063, and from 4.1 to 0 pg/mg protein, P = 0.031, respectively), and the concentrations of interleukin-13 and interferon-γ tended to increase (from 7.6 to 30.4 pg/mg protein, P = 0.078 and from 0 to 159.5 pg/mg protein, P = 0.031, respectively). These trends were typically similar at 12 months after transplantation. At a mean follow-up of 19.7 months, the survival rate was 75% and the freedom from bronchiolitis obliterans syndrome was 75%. Overall, the forced expiratory volume in 1 second remained stable during the first year after transplantation. CONCLUSIONS: Our preliminary study has demonstrated that LARS can restore the physiologic balance of pulmonary leukocyte populations and that the BALF concentration of pro-inflammatory mediators is altered early after LARS. These results suggest that LARS could modulate the pulmonary inflammatory milieu in lung transplant patients with gastroesophageal reflux disease.

How sticky? How tight? How hot? Imaging probes for fluid viscosity, membrane tension and temperature measurements at the cellular level.

We review the progress made in imaging probes for three important physical parameters: viscosity, membrane tension, and temperature, all of which play important roles in many cellular processes. Recent evidences showed that cell migration speed can be modulated by extracellular fluid viscosity; membrane tension contributes to the regulation of cell motility, exo-/endo-cytosis, and cell spread area; and temperature affects neural activity and adipocyte differentiation. We discuss the techniques implementing imaging-based probes to measure viscosity, membrane tension, and temperature at subcellular resolution dynamically. The merits and shortcomings of each technique are examined, and the future applications of the recently developed techniques are also explored.

Membrane Ruffling is a Mechanosensor of Extracellular Fluid Viscosity.

Cell behaviour is affected by the physical forces and mechanical properties of the cells and of their microenvironment. The viscosity of extracellular fluid - a component of the cellular microenvironment - can vary by orders of magnitude, but its effect on cell behaviour remains largely unexplored. Using bio-compatible polymers to increase the viscosity of the culture medium, we characterize how viscosity affects cell behaviour. We find that multiple types of adherent cells respond in an unexpected but similar manner to elevated viscosity. In a highly viscous medium, cells double their spread area, exhibit increased focal adhesion formation and turnover, generate significantly greater traction forces, and migrate nearly two times faster. We observe that when cells are immersed in regular medium, these viscosity-dependent responses require an actively ruffling lamellipodium - a dynamic membrane structure at the front of the cell. We present evidence that cells utilize membrane ruffling to sense changes in extracellular fluid viscosity and to trigger adaptive responses.

Bioinspired Materials with Self-Adaptable Mechanical Properties.

Natural structural materials, such as bone, can autonomously modulate their mechanical properties in response to external loading to prevent failure. These material systems smartly control the addition/removal of material in locations of high/low mechanical stress by utilizing local resources guided by biological signals. On the contrary, synthetic structural materials have unchanging mechanical properties limiting their mechanical performance and service life. Inspired by the mineralization process of bone, a material system that adapts its mechanical properties in response to external mechanical loading is reported. It is found that charges from piezoelectric scaffolds can induce mineralization from surrounding media. It is shown that the material system can adapt to external mechanical loading by inducing mineral deposition in proportion to the magnitude of the stress and the resulting piezoelectric charges. Moreover, the mineralization mechanism allows a simple one-step route for fabricating functionally graded materials by controlling the stress distribution along the scaffold. The findings can pave the way for a new class of self-regenerating materials that reinforce regions of high stress or induce deposition of minerals on the damaged areas from the increase in mechanical stress to prevent/mitigate failure. It is envisioned that the findings can contribute to addressing the current challenges of synthetic materials for load-bearing applications from self-adaptive capabilities.

3D-printed magnetic tweezers for dorsal traction force measurement.

In this study, economic magnetic tweezers (EMT) with a sharp gradient field were designed and built, in order to facilitate accurate force measurement. Our design costs less than 40 USD and is easy to mount onto most microscope stages. We leverage the computational fluidic dynamics techniques to calculate the forces based on the results obtained using our simple device. The EMT device is especially suitable to measure the traction forces at the dorsal side of a cell. As a proof of concept it was demonstrated that the EMT device could be applied to measure the dorsal traction forces exerted via the CD80-CTLA4 bond in metastatic cancer cells.

Laparoscopic treatment of epiphrenic diverticula: preoperative evaluation and surgical technique. How I do it.

INTRODUCTION: Traditionally, epiphrenic diverticula have been managed through a left thoracotomy. With the advancement of minimally invasive techniques, a laparoscopic approach has gained widespread popularity. Unfortunately, the preoperative evaluation of patients with epiphrenic diverticula, and their surgical management, is still not well characterized. DISCUSSION: The goal of this article is to illustrate our approach to patients with epiphrenic diverticula in terms of preoperative evaluation and surgical technique. The final discussion will focus on the evidence-based rationale for our preoperative assessment and surgical approach.