A minimal physical model for curvotaxis driven by curved protein complexes at the cell's leading edge.

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed "curvotaxis." The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a "minimal cell" model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.

A Change of Paradigm in the Management of Acute Psychiatric Episodes? A Retrospective Cohort Study on Trajectories of Use of Clinical Resources After the Implementation of Intensive Home-Treatment.

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (pBonf = 0.018) and with previous hospitalizations (pBonf < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (pBonf = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.

Connectivity and plasticity determine collagen network fracture.

Collagen forms the structural scaffold of connective tissues in all mammals. Tissues are remarkably resistant against mechanical deformations because collagen molecules hierarchically self-assemble in fibrous networks that stiffen with increasing strain. Nevertheless, collagen networks do fracture when tissues are overloaded or subject to pathological conditions such as aneurysms. Prior studies of the role of collagen in tissue fracture have mainly focused on tendons, which contain highly aligned bundles of collagen. By contrast, little is known about fracture of the orientationally more disordered collagen networks present in many other tissues such as skin and cartilage. Here, we combine shear rheology of reconstituted collagen networks with computer simulations to investigate the primary determinants of fracture in disordered collagen networks. We show that the fracture strain is controlled by the coordination number of the network junctions, with less connected networks fracturing at larger strains. The hierarchical structure of collagen fine-tunes the fracture strain by providing structural plasticity at the network and fiber level. Our findings imply that low connectivity and plasticity provide protective mechanisms against network fracture that can optimize the strength of biological tissues.

Cultural and translation challenges in assessing health literacy among immigrants from the former Soviet Union.

Health literacy is an important foundation for health promotion and an under-recognized risk factor for immigrant and refugee groups. Yet measuring health literacy among diverse ethnic and linguistic populations presents complex challenges. We describe cultural and translation challenges encountered in measuring health literacy among Russian-speaking immigrants to the USA and offer a mixed-methods approach to understanding them. The Rx-Health Literacy (RxHL) study used cross-sectional quantitative and qualitative data to examine health literacy and medication adherence among five cultural and four language groups (Latinx, Vietnamese, African-American, Russian-speaking immigrant and White American) who are patients at Caring Health Center, a federally qualified health center in Springfield, MA. We translated an existing health literacy scale into Russian and Vietnamese and examined item difficulty across cultural groups. We conducted qualitative cognitive interviews to learn more about Russian speakers' understandings of the scale. Health literacy scores varied by cultural group, and the range of correct responses was much greater among Russian speakers than in other groups. Percentage correct varied by 69.7% for Russian speakers, compared with 25.0-44.0% for other groups. These findings indicate greater variability in health literacy levels among this group compared with others. Cognitive interviews with Russian-speaking participants revealed multiple interpretations of several items, suggesting that the English version of the scale contained embedded meanings associated with an American health care context that were not captured in the translated instrument. Combining qualitative and quantitative research methods allows for greater insight into contextual and translation factors that may shape the results of translated instruments in unanticipated ways.

High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner.

Long-term high-fat diet (HFD) consumption commonly leads to obesity, a major health concern of western societies and a risk factor for Alzheimer's disease (AD). Both conditions present glial activation and inflammation and show sex differences in their incidence, clinical manifestation, and disease course. HFD intake has an important impact on gut microbiota, the bacteria present in the gut, and microbiota dysbiosis is associated with inflammation and certain mental disorders such as anxiety. In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis-related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time in the tail suspension test, with increased defecation. Intriguingly, female TgAPP mice on HFD showed less immobility and defecation compared to female WT mice on HFD. HFD induced dysbiosis of gut microbiota, resulting in reduced microbiota diversity and abundance compared with LFD fed mice, with some significant differences due to sex and little effect of genotype. Gene expression of pro-inflammatory/phagocytic markers in the hippocampus were not different between male and female WT mice, and in TgAPP mice of both sexes, some cytokines (IL-6 and IFNγ) were higher than in WT mice on LFD, more so in female TgAPP (IL-6). HFD induced few alterations in mRNA expression of inflammatory/phagocytosis-related genes in male mice, whether WT (IL-1ß, MHCII), or TgAPP (IL-6). However, in female TgAPP, altered gene expression returned towards control levels following prolonged HFD (IL-6, IL-12ß, TNFα, CD36, IRAK4, PYRY6). In summary, we demonstrate that HFD induces anxiogenic symptoms, marked alterations in gut microbiota, and increased expression of inflammatory genes, except for female TgAPP that appear to be resistant to the diet effects. Lifestyle interventions should be introduced to prevent AD onset or exacerbation by reducing inflammation and its associated symptoms; however, our results suggest that the eventual goal of developing prevention and treatment strategies should take sex into consideration.

COVID-19 mitigation for high-risk populations in Springfield Massachusetts USA: a health systems approach.

BACKGROUND: Numerous reports have demonstrated the disproportionate impact that COVID-19 has had on vulnerable populations. Our purpose is to describe our health care system's response to this impact. METHODS: We convened a Workgroup with the goal to mitigate the impact of COVID-19 on the most medically vulnerable people in Springfield, Massachusetts, USA, particularly those with significant social needs. We did this through (1) identifying vulnerable patients in high-need geographic areas, (2) developing and implementing a needs assessment/outreach tool tailored to meet cultural, linguistic and religious backgrounds, (3) surveying pharmacies for access to medication delivery, (4) gathering information about sources of food delivery, groceries and/or prepared food, (5) gathering information about means of travel, and (6) assessing need for testing. We then combined these six elements into a patient-oriented branch and a community outreach/engagement branch. CONCLUSIONS: Our highly intentional and methodical approach to patient and community outreach with a strong geographic component has led to fruitful efforts in COVID-19 mitigation. Our patient-level outreach engages our health centers' clinical teams, particularly community health workers, and is providing the direct benefit of material and service resources for our at-risk patients and their families. Our community efforts leveraged existing relationships and created new partnerships that continue to inform us-healthcare entities, healthcare employees, and clinical teams-so that we can grow and learn in order to authentically build trust and engagement.

Surgery and Radiosurgery in Autism: A Retrospective Study in 10 Patients.

INTRODUCTION: A subgroup of patients with autism spectrum disorder (ASD) show self or heteroaggression, dyscontrol episodes, and others are of obsessive-compulsive disorder (OCD) profile; some of them are resistant to medical and behavioural treatment. We describe the long-term outcome in a group of these patients, treated with radiofrequency brain lesions or combined stereotactic surgery and Gamma Knife (GK) radiosurgery. METHODS: We reviewed the medical records of 10 ASD patients with pathological aggressiveness and OCD, who had undergone radiofrequency lesions and/or radiosurgery with GK in our institution. RESULTS: The 10 patients had a significant reduction of their symptoms (PCQ 39.9 and 33, OAS 11.8 and 5, CYBOCS-ASD 30.4 and 20), preoperatively and in the last follow-up, respectively; p < 0.005 (in all cases), although all but 2 needed more than 1 treatment to maintain this improvement. CONCLUSIONS: We observed a marked improvement in behaviour, quality of life, and relationship with the environment in all our 10 patients after the lesioning treatments, without long-lasting side effects.

Label-Free Mass Spectrometry-Based Quantification of Linker Histone H1 Variants in Clinical Samples.

Epigenetic aberrations have been recognized as important contributors to cancer onset and development, and increasing evidence suggests that linker histone H1 variants may serve as biomarkers useful for patient stratification, as well as play an important role as drivers in cancer. Although traditionally histone H1 levels have been studied using antibody-based methods and RNA expression, these approaches suffer from limitations. Mass spectrometry (MS)-based proteomics represents the ideal tool to accurately quantify relative changes in protein abundance within complex samples. In this study, we used a label-free quantification approach to simultaneously analyze all somatic histone H1 variants in clinical samples and verified its applicability to laser micro-dissected tissue areas containing as low as 1000 cells. We then applied it to breast cancer patient samples, identifying differences in linker histone variants patters in primary triple-negative breast tumors with and without relapse after chemotherapy. This study highlights how label-free quantitation by MS is a valuable option to accurately quantitate histone H1 levels in different types of clinical samples, including very low-abundance patient tissues.

Effects of Diabetes Mellitus on Fibrin Clot Structure and Mechanics in a Model of Acute Neutrophil Extracellular Traps (NETs) Formation.

Subjects with diabetes mellitus (DM) have an increased risk of arterial thrombosis, to which changes in clot structure and mechanics may contribute. Another contributing factor might be an increased formation of neutrophil extracellular traps (NETs) in DM. NETs are mainly formed during the acute phase of disease and form a network within the fibrin matrix, thereby influencing clot properties. Previous research has shown separate effects of NETs and DM on clot properties, therefore our aim was to study how DM affects clot properties in a model resembling an acute phase of disease with NETs formation. Clots were prepared from citrated plasma from subjects with and without DM with the addition of NETs, induced in neutrophils by S. aureus bacteria or phorbol myristate acetate (PMA). Structural parameters were measured using scanning electron microscopy, mechanical properties using rheology, and sensitivity to lysis using a fluorescence-based fibrinolysis assay. Plasma clots from subjects with DM had significantly thicker fibers and fewer pores and branch points than clots from subjects without DM. In addition, fibrinolysis was significantly slower, while mechanical properties were similar between both groups. In conclusion, in a model of acute NETs formation, DM plasma shows prothrombotic effects on fibrin clots.

The RxHL study: community-responsive research to explore barriers to medication adherence.

This study aims to contribute to the development of community-responsive research approaches by describing the research methods used in the RxHL study and the interprofessional and community-based collaboration that produced them. The mixed-method RxHL study was developed in close consultation with staff and providers at our research site, a federally qualified health center in Springfield, MA. We utilized quantitative methods including chart review, manual pill counts and self-report surveys to assess factors associated with medication adherence in a diverse population of low-income patients with chronic disease. We triangulated these results with findings from qualitative methods that included in-depth interviews, home visits and chronic disease diaries. We used the constant comparison method and interdisciplinary, participatory team meetings to integrate quantitative and qualitative findings. A community-responsive approach facilitated the recruitment and retention of a diverse sample of patients. Self-report surveys revealed the widespread scope of barriers to care such as medication costs and transportation, and limited health literacy among diverse groups. Qualitative research methods offered a deeper understanding of the social and environmental contexts in which medication adherence takes place. Prioritizing the needs of community partners and research participants facilitates rigorous data collection in clinical settings with maximum participation from community partners.

Traumatic atlantoaxial rotatory fixation in an adult patient.

INTRODUCTION: Atlantoaxial rotational fixation (AARF) is a rare entity in adults, with only a few cases reported in the English literature and often associated with a traumatic mechanism. It is an underdiagnosed condition that must be taken into account in the initial assessment of all craniocervical trauma. Both diagnostic and therapeutic delay may be a potential cause of severe neurological damage or even death of the patient. The therapeutic management is controversial given the difficulty of achieving optimum stability and permanent reduction. METHODS AND RESULTS: A 28-year-old woman was involved in a traffic accident a week before coming to the emergency with rotation and irreducible cervical flexion from trauma and severe neck pain. CT and MRI column were performed and showed a cervical spinal AARF with transverse and alar ligaments intact and preserved atlantoaxial distance (Fielding I). The patient was treated by progressive cervical traction with 5 kg and manual reduction was completed in 24 h. Subsequently, an external immobilization was performed by cervical rigid collar for 16 weeks. The clinical course was good, with the patient regaining full mobility with cervical neck pain improvement. CONCLUSIONS: The purpose of this paper is to show a case of a young woman with a posttraumatic AARF successfully treated conservatively. This case delineates the difficulties in diagnosing this pathology, as well as the challenges encountered in its management.

Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome After Acute Stroke.

Background and Purpose- Physiological effects of stroke are best assessed over entire brain networks rather than just focally at the site of structural damage. Resting-state functional magnetic resonance imaging can map functional-anatomic networks by analyzing spontaneously correlated low-frequency activity fluctuations across the brain, but its potential usefulness in predicting functional outcome after acute stroke remains unknown. We assessed the ability of resting-state functional magnetic resonance imaging to predict functional outcome after acute stroke. Methods- We scanned 37 consecutive reperfused stroke patients (age, 69±14 years; 14 females; 3-day National Institutes of Health Stroke Scale score, 6±5) on day 3 after symptom onset. After imaging preprocessing, we used a whole-brain mask to calculate the correlation coefficient matrices for every paired region using the Harvard-Oxford probabilistic atlas. To evaluate functional outcome, we applied the modified Rankin Scale at 90 days. We used region of interest analyses to explore the functional connectivity between regions and graph-computation analysis to detect differences in functional connectivity between patients with good functional outcome (modified Rankin Scale score ≤2) and those with poor outcome (modified Rankin Scale score >2). Results- Patients with good outcome had greater functional connectivity than patients with poor outcome. Although 3-day National Institutes of Health Stroke Scale score was the most accurate independent predictor of 90-day modified Rankin Scale (84.2%), adding functional connectivity increased accuracy to 94.7%. Preserved bilateral interhemispheric connectivity between the anterior inferior temporal gyrus and superior frontal gyrus and decreased connectivity between the caudate and anterior inferior temporal gyrus in the left hemisphere had the greatest impact in favoring good prognosis. Conclusions- These data suggest that information about functional connectivity from resting-state functional magnetic resonance imaging may help predict 90-day stroke outcome.

Effect of ionic strength on the structure and elongational kinetics of vimentin filaments.

Intermediate filaments are a major structural element in the cytoskeleton of animal cells that mechanically integrate other cytoskeletal components and absorb externally applied stress. Their role is likely to be linked to their complex molecular architecture which is the product of a multi-step assembly pathway. Intermediate filaments form tetrameric subunits which assemble in the presence of monovalent salts to form unit length filaments that subsequently elongate by end-to-end annealing. The present work characterizes this complex assembly process using reconstituted vimentin intermediate filaments with monovalent salts as an assembly trigger. A multi-scale approach is used, comprising static light scattering, dynamic light scattering and quantitative scanning transmission electron microscopy (STEM) mass measurements. Light scattering reveals the radius of gyration (Rg), molecular weight (Mw) and diffusion coefficient (D) of the assembling filaments as a function of time and salt concentration (cS) for the given protein concentration of 0.07 g L-1. At low cS (10 mM KCl) no lateral or elongational growth is observed, whereas at cS = 50-200 mM, the hydrodynamic cross-sectional radius and the elongation rate increases with cS. Rgversus Mw plots suggest that the mass per unit length increases with increasing salt content, which is confirmed by STEM mass measurements. A kinetic model based on rate equations for a two step process is able to accurately describe the variation of mass, length and diffusion coefficient of the filaments with time and provides a consistent description of the elongation accelerated by increasing cS.

What information and the extent of information research participants need in informed consent forms: a multi-country survey.

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration.

We wanted to analyze whether tumor HLA class I (HLA-I) expression influences the pattern of the immune cell infiltration and stromal cell reaction in the tumor microenvironment. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. 28 patients out of the 57 were completely negative for HLA-I expression (49.1%) or showed a selective HLA-A locus downregulation (three patients, 5.2%). In 26 out of 57 tumors (47.8%) we detected a positive HLA-I expression but with a percentage of HLA-I negative cells between 10 and 25%. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of ß2-microglobulin (ß2-m) and LMP2 and LMP7 antigen presentation machinery genes. The analysis and localization of different immune cell populations revealed the presence of two major and reproducible patterns. One pattern, which we designated "immune-permissive tumor microenvironment (TME)," was characterized by positive tumor HLA-I expression, intratumoral infiltration with cytotoxic T-CD8+ cells, M1-inflammatory type macrophages, and a diffuse pattern of FAP+ cancer-associated fibroblasts. In contrast, another pattern defined as "non-immune-permissive TME" was found in HLA-I negative tumors with strong stromal-matrix interaction, T-CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair-type macrophages. In conclusion, this study revealed marked differences between HLA class I-positive and negative tumors related to tissue structure, the composition of leukocyte infiltration and stromal response in the tumor microenvironment.

Effectiveness of vagal nerve stimulation in medication-resistant epilepsy. Comparison between patients with and without medication changes.

BACKGROUND: Vagal nerve stimulation (VNS) response is not immediate. A progressive decline in seizure frequency is usually found during a period of 12-18 months after implantation. During this time, the patient's medication is usually modified, which can create doubts about whether their clinical improvement is due to medication changes or to VNS itself. Our goal is to compare two groups of patients treated with VNS, with and without changes in their medication. METHODS: We prospectively analyze 85 patients who were treated with VNS in our hospital between 2005 and 2014. In 43 patients, changes in the antiepileptic drugs (EAD) were not allowed during the postoperative follow-up and they were compared with 42 patients who were left at the option of neurologist make changes in medication. We analyzed the clinical situation at 18 months and compared the two groups. RESULTS: Overall, 54.1% of patients had a reduction in seizures of 50% or higher (responders). In the group with no changes in medication, responders reached 63%, while in the group in which changes in medication were allowed, 45.2% were responders. Between responders and non-responders, there were no statistical differences in type of epilepsy, frequency, previous surgery, or intensity of stimulation. CONCLUSIONS: We did not find a statistical difference in seizure frequency reduction between patients with or without changes in medication during their follow-up, so changes in medication did not improve the outcome. Furthermore, the absence of changes in AED can help to optimize the parameters of the stimulator in order to improve its effectiveness.

Time-lapse scanning surface plasmon microscopy of living adherent cells with a radially polarized beam.

We report on a fibered high-resolution scanning surface plasmon microscope for long term imaging of living adherent cells. The coupling of a high numerical aperture objective lens and a fibered heterodyne interferometer enhances both the sensitivity and the long term stability of this microscope, allowing for time-lapse recording over several days. The diffraction limit is reached with a radially polarized illumination beam. Adherence and motility of living C2C12 myoblast cells are followed for 50 h, revealing that the dynamics of these cells change after 10 h. This plasmon enhanced evanescent wave microscopy is particularly suited for investigating cell adhesion, since it can not only be performed without staining of the sample but it can also capture in real time the exchange of extracellular matrix elements between the substrate and the cells.

The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.

Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development, and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb target genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants, supporting a functional interplay between Polycomb proteins and Jarid1b. To understand how Jarid1b regulates mouse development, we performed a genome-wide analysis of histone modifications, which demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 during early embryogenesis in Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators like Pax6 and Otx2 in Jarid1b knockout brains. Taken together, these results suggest that Jarid1b regulates mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications.

Single Cell Wall Nonlinear Mechanics Revealed by a Multiscale Analysis of AFM Force-Indentation Curves.

Individual plant cells are rather complex mechanical objects. Despite the fact that their wall mechanical strength may be weakened by comparison with their original tissue template, they nevertheless retain some generic properties of the mother tissue, namely the viscoelasticity and the shape of their walls, which are driven by their internal hydrostatic turgor pressure. This viscoelastic behavior, which affects the power-law response of these cells when indented by an atomic force cantilever with a pyramidal tip, is also very sensitive to the culture media. To our knowledge, we develop here an original analyzing method, based on a multiscale decomposition of force-indentation curves, that reveals and quantifies for the first time the nonlinearity of the mechanical response of living single plant cells upon mechanical deformation. Further comparing the nonlinear strain responses of these isolated cells in three different media, we reveal an alteration of their linear bending elastic regime in both hyper- and hypotonic conditions.

Preoperative predictors of pathological lymph node metastasis in patients with renal cell carcinoma undergoing retroperitoneal lymph node dissection.

PURPOSE: Patients with locally advanced renal cell carcinoma represent a subset that may benefit from retroperitoneal lymph node dissection. We identified preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma without distant metastasis who underwent retroperitoneal lymph node dissection. MATERIALS AND METHODS: We retrospectively analyzed data on a consecutive cohort of 1,270 patients with cTany Nany M0 renal cell carcinoma who were treated at a single institution from 1993 to 2012. Multivariate analysis was performed to determine preoperative predictors of pathologically positive lymph nodes in patients who underwent retroperitoneal lymph node dissection. A nomogram was developed to predict the probability of lymph node metastasis. Overall, cancer specific and recurrence-free survival was estimated using the Kaplan-Meier Method. RESULTS: We identified 1,270 patients with renal cell carcinoma without distant metastasis who had (564) or did not have (706) retroperitoneal lymph node dissection performed. Of the 564 patients 131 (23%) and 433 (77%) had pN1 and pN0 disease, and 60 (37%) and 29 (7.2%) had cN1pN0 and cN0pN1 disease, respectively. ECOG PS, cN stage, local symptoms and lactate dehydrogenase were associated with nodal metastasis on multivariable analysis. A nomogram was developed with a C-index of 0.89 that demonstrated excellent calibration. Differences in overall, cancer specific and recurrence-free survival among pNx, pN0 and pN1 cases were statistically significant (p <0.001). CONCLUSIONS: Local symptoms, ECOG PS, cN stage and lactate dehydrogenase were independent predictors of lymph node metastasis in patients who underwent retroperitoneal lymph node dissection. Our predictive nomogram using these factors showed excellent discrimination and calibration.