The alveolar subtype

has a gross appearance of more circu

The alveolar subtype

has a gross appearance of more circumscribed edges and a firmer, more rounded consistency. Microscopically, these tend to contain rounded, small acidophilic cells septated by collagen tissue with a broken off appearance with occasional giant cell formation. They tend to have larger nuclei and heavier chromatin patterns than embryonal types. Immunohistochemical profiling Inhibitors,research,lifescience,medical is the same as embryonal but staining for anti-skeletal muscle antibody and S100 protein was also documented (42,43). A study of 24 RMS of different types, showed all cases staining positively for Ankyrin-Repeated Proteins “Arpp/Carp” (44). RMS is harder to diagnose in adults, with more advanced disease at presentation (34). This may be due to the fact that symptoms

(tenesmus, pain on defecation or Inhibitors,research,lifescience,medical fever along with mild leukocytosis in some cases) tend to present later, probably because of a larger space for the tumor to grow. There is also a higher risk of misdiagnosis with diseases of infectious or inflammatory origin, such as perianal abscesses (45-47). In addition, younger patients and especially infants tend to be examined more often by parents during diaper Inhibitors,research,lifescience,medical changes possibly explaining why RMS is picked up earlier (34). The mainstay of RMS treatment is resection to negative margins and a combination of chemotherapy and radiation therapy. Pediatric RMS guidelines state that microscopically negative margins should be obtained and ipsilateral lymph node basins (inguinal, selleck screening library retroperitoneal) should be excised in patients older than 10 years. Although unproven, these guidelines have been used for treating Inhibitors,research,lifescience,medical adults as well. The use of chemotherapy combining Vincristine, Actinomycin D, Cyclophosphamide and Adriamycin in conjunction with external beam Tipifarnib radiotherapy for patients with positive margins, and local node involvement has also been advocated (34). However, radiotherapy Inhibitors,research,lifescience,medical is often associated with dermopathy, anal stenosis and genitourinary complications (48). Because aggressive surgery often results in sacrificing

the function of the anorectum, Dacomitinib sporadic attempts have been made at neoadjuvant chemotherapy to reduce tumor size and improve resectability. Intraoperative radiation therapy also has been sporadically used. Twelve adult cases of anorectal RMS have been reported (45-47,49-56), ranging between the ages of 18 and 71. Seven patients had radical surgery (APR or anterior resection), three had local excision and two never underwent an operation (patient refusal and bony metastasis at presentation. Half the patients had adjuvant chemoradiation with a combination of Vincristine, Actinomycin-D, Adriamycin and/or ifosfamide. Neoadjuvant therapy was used in two patients. Ten of the twelve cases had follow up data reported. Among these, 3 patients recurred within 6 months of surgery.

These range from relatively specific agonists at GABAb receptors,

These range from relatively specific agonists at GABAb receptors, such as baclofen, which inhibit synaptic glutamate release to a host of less selective compounds known to increase GABA transmission via interactions with synthetic or selleck chemical Palbociclib elimination mechanisms, such as topiramate or vigabatrin. For all of these compounds there is preclinical and clinical data to support some potential efficacy.79-85 However, as fda approved predicted, especially for the Inhibitors,research,lifescience,medical nonselective GABAmimetics untoward side effects, such as sedation, are reported. Conclusions This review has endeavored to transport the reader

from the initiating molecular actions of amphetamine-like psychostimulants on dopamine systems in the brain to enduring neuroplasticity produced in glutamate transmission responsible for communicating from prefrontal and allocortical brain Inhibitors,research,lifescience,medical regions through the nucleus accumbens to motor regulatory systems. Moreover, by examining molecular neuroplasticity produced in excitatory synapses by chronic psychostimulant administration, it is possible to make some

deductions about potential pharmacotherapeutic Inhibitors,research,lifescience,medical interventions. Indeed, there already exists an emerging literature supporting this approach in developing potential pharmacotherapies for treating psychostimulant addiction. Importantly, this is a nascent and emerging science, and while much has been discovered, the cutting edge of discovery into the neuroplasticity produced by psychostimulants is understandably contradictory. As further discoveries are made that allow us to understand the nature of these contradictions, it should follow that additional targets will emerge to provide potential novel pharmacotherapies for treating psychostimulant Inhibitors,research,lifescience,medical addiction. Selected abbreviations and acronyms AMPA α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid DAT dopamine transporters GABA γ-aminobutyric acid MDMA 3,4-methylenedioxymethamphetamine Inhibitors,research,lifescience,medical mGluR2/3 metabotropic glutamate receptors Notes A portion of the research described in this article was supported by Batimastat USPHS grants DA03906, DA12513, “type”:”entrez-nucleotide”,”attrs”:”text”:”DA015851″,”term_id”:”78414989″,”term_text”:”DA015851″DA015851,

DA11809 and “type”:”entrez-nucleotide”,”attrs”:”text”:”DA015369″,”term_id”:”78410917″,”term_text”:”DA015369″DA015369.
Alcoholism is a chronic and relapsing disorder that imposes enormous costs on society, is one of the leading causes of death in industrialized countries, and is among the strongest cost drivers with respect to service use.1-5 Thus, the development of successful treatment approaches and their intensive analysis is of major importance for public health. Alcohol dependence is one of the most frequent psychiatric disorders, with a 12-month prevalence of at least 3%, a lifetime prevalence of 8% to 14%, and a maleifemale ratio of 2-5:1.

Secondary outcomes included the efficacy of the treatment regimen

Secondary outcomes included the efficacy of the treatment regimen [objective response rate, disease control rate, progression-free survival (PFS), overall survival, duration of response] and the safety of combination therapy. An exploratory objective evaluated the association between tumor EGFR and COX-2 immuno-expression and tumor response. The trial was conducted in accordance with Good Clinical Practice and the ethical principles outlined in the revised Declaration of Helsinki. Local ethics committee approval was obtained before study initiation and all participants

gave written, informed consent. Eligible patients were administered gefitinib and celecoxib, both given orally, from day 1 Inhibitors,research,lifescience,medical until disease progression, unacceptable toxicity, or withdrawal. Wherever possible, patients were followed up for ≥6 months after the start of trial therapy, with assessment on day

15 and then every 28 days thereafter. Safety and tolerability measures The nature, Inhibitors,research,lifescience,medical incidence, and severity of adverse events (AEs) were recorded throughout the study. Routine hematology, biochemistry, and physical examinations were carried out during the seven days before study entry and during the treatment phase on day 1, day 15, and every 28 days thereafter. Urinalysis Inhibitors,research,lifescience,medical was performed as necessary. Both AEs and laboratory parameters were assessed using National Cancer Romidepsin side effects Institute CTC version 2.0. Causality was assigned by the investigators. In cases where toxicity was unacceptable, dose

interruptions (≤14 days) were used as the first approach to manage toxicity. Repeat dose interruptions were permitted but if toxicity recurred on re-challenge and further Inhibitors,research,lifescience,medical interruptions were not considered to be sufficient to resolve toxicity, patients were either withdrawn from the study (for gefitinib-related toxicities) or underwent a dose reduction (for celecoxib-related toxicities). A single celecoxib dose reduction (from 400 to 200 mg bid) was permitted in patients experiencing recurring toxicity (> grade 2) to celecoxib. However, if serious GI toxicity was observed, celecoxib Inhibitors,research,lifescience,medical was discontinued and patients could continue on gefitinib monotherapy. Efficacy measures Objective tumor response (complete or partial response) was evaluated using RECIST within the 3 weeks prior to study entry, 6 weeks after the start of therapy, and every 12 weeks thereafter until disease progression. Patients were considered to have controlled disease if the RECIST criteria Entinostat for complete response, partial response, or stable disease were at any time satisfied at or before trial closure. The duration of response was defined as the number of days from the first documented response until death/progression or the last on-study tumor assessment. Likewise, time to progression (TTP) was defined as the number of days from start of treatment on day 1 until disease progression/death or the last tumor assessment.

The mean fluorescence intensity of the cells isolated from the p

The mean fluorescence intensity of the cells isolated from the peritoneal cavity 20 or 60hrs after the administration was 4.78 or 47.61 per 10000 cells, respectively. The calculated concentration of Hoechst 33342 was 40.1ng/mL after 20hrs or 491.0ng/mL after 60hrs. Figure 8 (a) Fluorescence intensity of U-937 cells was analyzed after

staining with serial concentrations of Hoechst 33342 using FACS Aria II. The segments P1, P2, P3, or P4 correspond to the range of fluorescence intensity at 0, 10, 100, or 1000ng/mL … In the present study we have used Hoechst 33342-incorporated PLGA to identify, isolate, and characterize cells exposed to this Inhibitors,research,lifescience,medical fluorescent dye. The nuclear staining of Hoechst 33342 in vivo is a powerful marker for the isolation of cells from blood, ascites, LY317615 pleural effusions, and even tissues when the tissue dissociation

and cell isolation protocol is established. In addition, we can also collect cells that are negative for fluorescence. Once the various cells have Inhibitors,research,lifescience,medical been isolated, they can be analyzed for cell type and expression of specific molecules such as surface markers that may be important in cell targeting. One major limitation of the present approach is that Hoechst 33342 used as an imitating drug will be different from the actual drug in terms of molecular weight, structure, electrical charge, and/or presence/absence of specificity Inhibitors,research,lifescience,medical for a target molecule. Nonetheless, the present approach is useful for investigating the likely distribution of released Inhibitors,research,lifescience,medical materials from individual PLGA particles in the microenvironment of target tissues. 4. Conclusion The present study successfully demonstrated that Hoechst 33342-incorporated PLGA particles can be used to simulate the drug exposure of cells in Inhibitors,research,lifescience,medical situ. We isolated cells exposed to this fluorescent dye as well as those that were not. These two classes of cells can then be further characterized, especially with regard to the expression of specific molecules that may be important in the targeting mechanism. The present approach may provide

essential information concerning cell targeting in any type of PLGA DDS. Conflict of Interests The authors certify that there is no conflict of interest’s with any financial organization regarding the material discussed in the paper. Acknowledgments The study Cilengitide was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and a grant from the Intractable Diseases, the Health and Labor, and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan. Some of the results were generated by using the facilities of Biomedical Research Core of Tohoku University Graduate School of Medicine. The authors also acknowledge the support of Tohoku University Global COE Program “Global Nano-Biomedical Engineering kinase inhibitor Imatinib Education and Research Network Centre.

The ability of network theories to predict functional output from

The ability of network theories to predict functional output from ensembles of individual noisy and unreliable elements is (most often) demonstrated numerically

or (rarely) derived analytically under severely limiting simplifications. However, the simplified network units used in these theoretical studies are remote from the richness of biological neuronal entities, the complexity of their networks, and their interactions with the environment. Thus most neuronal network concepts are yet to be tested experimentally in physiological settings. Inhibitors,research,lifescience,medical This state-of-the-art points towards an acute need for controlled multi-level experimental access to large networks of real neurons over the wide range of relevant time and length scales (milliseconds to weeks; micrometers to millimeters). An ideal experimental system should serve both as a source for fresh insights as well as a natural test bed for verification or modification of existing theories. What are the requirements from an experimental network system? The system should Inhibitors,research,lifescience,medical allow for references simultaneous stimulation and recordings from many individual neurons and individual synapses; long-term monitoring Inhibitors,research,lifescience,medical and manipulation of both activity and structure

over the wide range of relevant time and length scales; enforcement of developmental constraints at both the structural and functional levels; access to chemical modulation; and controllability of connection between elements as well as between ensembles. Such omni-potentiality is practically impossible at the level of behaving organisms or in

preparations where preformed structures are examined in vitro (e.g. brain slices). Here we review the use of multi-site interaction with large cortical networks Inhibitors,research,lifescience,medical developing ex vivo, in a culture dish, to study basic biophysical aspects of synchronization, adaptation, learning, and representation Inhibitors,research,lifescience,medical in neuronal assemblies. Out of various alternatives, large, random, cultured networks of cortical neurons developing ex vivo are most appropriate experimental model systems for studying the general questions of learning and memory at the population level. An extensive survey of the properties of large, random, cortical networks developing ex vivo may be found in recent reviews.2,3 These Entinostat networks are relatively free of predefined constraints and intervening variables, yet the electrophysiological, biochemical, and pharmacological properties of their neurons are by and large identical to neurons in vivo.4–9 The proportions of different cell types are practically identical to those found in vivo.10–12 Unlike slice preparations, the ex vivo developing networks are not cut out of a larger system to which their structures are particularly fitted, and in the absence of which they might function aberrantly. Indeed, alternative models, such as acute cortical selleck inhibitor slices and cultured slices, allow one to explore “what is there”, but not “how it got to be there”.

45–47 Similar stability of

45–47 Similar stability of Paclitaxel imaging characteristics were reported from 30 minutes to 12 hours following ablation, though the lesion check details contrast by T1-weighted imaging appears to be less than for T2-weighted imaging.46

Gadolinium delayed enhancement CMR (DECMR) can provide better visualization of RF ablation lesions compared with non-contrast imaging techniques (Figure 6). The time to achieve full enhancement of RF ablation lesions, 1 to 2 hours, is considerably longer than Inhibitors,research,lifescience,medical for DECMR of myocardial infarct scar.48 However, good correlation with pathologic lesion size was noted for intermediate enhancement patterns from 1 minute to 2 hours after contrast injection, allowing lesion extent to be assessed without waiting for full enhancement.48 The 1 to 2 hour interval Inhibitors,research,lifescience,medical required for renal clearance between repeated dosing of gadolinium and the ceiling on total allowable gadolinium dose limit the use of this technique for serial lesion assessment during a procedure.45 Still, gadolinium-enhanced imaging may be useful for evaluating gaps in ablation

lines after completion of a procedure to assess the need to place additional lesions. Figure 6 Example of gadolinium-enhanced T1-weighted MR imaging of right ventricular epicardial RF ablation lesions with pathologic correlation. Inhibitors,research,lifescience,medical Different lesion enhancement patterns are seen from 1 minute to 2 hours after contrast injection. Figure included with … Other methods for monitoring ablation lesion formation during RF energy application are also being investigated. Proton resonance shift thermography is an MRI technique that takes advantage of the decrease in the proton resonance frequency with increasing temperature.49 This technique Inhibitors,research,lifescience,medical has been used to follow tumor ablation in the uterus, liver, prostate, and brain using diverse energy sources including RF, high-frequency ultrasound, laser, and microwave.50–55 Its use for following RF ablation in the beating heart is being investigated. Current-vector mapping

Inhibitors,research,lifescience,medical has also been described for monitoring the extent of tissue power deposition during RF ablation.56 While most cardiac ablation lesion MRI studies have been performed in roughly 10 mm thick ventricle, imaging the less than 3 mm thick human atria is of particular clinical interest given the difficulty of achieving long-term pulmonary GSK-3 vein isolation following atrial fibrillation ablation. Peters et al. demonstrated 3-D DECMR of left atrial ablation lesions 10 to 15 minutes after contrast injection using image-based respiratory gating.24 This gating technique, also known as respiratory navigator imaging, allowed higher-resolution 3-D imaging to be performed without the need for prolonged breath-holding by tracking diaphragm position on fast 1-D images and collecting 3-D image data within a narrow range of diaphragm positions. Current applications have used a roughly 100 ms mid-diastolic acquisition window timed to precede atrial systole to reduce atrial motion during imaging. Image resolutions of 1.25 × 1.25 × 2.

It is amazing to see how Letourneau’s views on emotions, more th

It is amazing to see how Letourneau’s views on emotions, more than a century ago, were in many ways premonitory. The fact that tech support emotions are “intimately linked with organic life,” his precise description of the sequence of the physiological and behavioral reactions that accompany a strong emotion, such as fear, the idea that emotions involve specific areas of the brain, and the theory that activation of these areas is associated with an increased blood flow have all been largely confirmed by modern neuroscience. The suggestion that temperament or personality traits influence the “affective Inhibitors,research,lifescience,medical style” and vulnerability to psychopathology is also an important

aspect of our modern approach to anxiety and mood disorders.2 For a long time, emotions were considered to be unique to human beings, and were studied mainly from a philosophical perspective.3 Inhibitors,research,lifescience,medical Evolutionary theories and progress in brain and behavioral

research, physiology, and psychology have progressively introduced the study of emotions into the field of biology, and understanding the mechanisms, functions, and evolutionary significance of emotional processes is becoming a major goal of modem neuroscience. Inhibitors,research,lifescience,medical Three fundamental aspects of emotions The modem era of emotion selleck chemical research probably started when it became obvious that emotions are not just “feelings” or mental states, but are accompanied by physiological and behavioral changes that are an integral part of them. This has progressively led to today’s view of emotions being experienced or expressed at Inhibitors,research,lifescience,medical three different, but closely interrelated levels: the mental or psychological level, the (neuro)physiological level, and the behavioral Inhibitors,research,lifescience,medical level. These three complementary aspects are present in even the most basic emotions, such as fear. A detailed account of the many “theories of emotion” is beyond the scope of this review. However, a brief historical survey of the more biologically

oriented ones may help to set some important conceptual issues.3-8 One of the main questions addressed by earlier scientific theories of emotions was whether physiological changes precede the emotional experience, or if they are Dacomitinib only a consequence of it. For James (1884) and Lange (1885), “[...] the bodily changes follow directly the perception of the existing fact, and [...] our feelings of the same changes as they occur IS the emotion.” In other words, according to the James-Lange theory of emotions, stimuli reaching the cerebral cortex induce visceral changes, which are then perceived as emotion. Cannon and Bard (1915-1932) criticized this theory and proposed that the neurophysiological aspects of emotions are subcortical and involve the thalamus.

He et al assessed the diagnostic and prognostic value of circulat

He et al assessed the diagnostic and prognostic value of circulating miR-328 and -134 in AMI selleck product patients.To this aim, this group performed qPCR in plasma samples of 359 AMI patients and 30 healthy volunteers, and in parallel measured high-sensitivity cardiac troponin T (hs-cTnT) levels. Whilst miR-328 and -134 plasma levels were found to be significantly higher in patients in comparison to healthy controls, the diagnostic value of these miRs as determined by ROC curve analysis was significant, but inferior to (hs-cTnT) levels for AMI diagnosis. Interestingly though, the levels of these two circulating miRNAs were found

to be associated with the risk of mortality and development of HF within 6 months after infarction (miR-328: OR 7.35, 95 % confidence interval 1.07-17.83, P < 0.001, miR-134: OR 2.28, 95 % confidence interval 1.03-11.32 P < 0.001). 183 As such, miR-328 and 134 could be utilized as prognostic markers of post AMI clinical outcome. Qiang et al investigated the miRNA expression profiles of endothelial progenitor cells (EPCs) isolated from venous blood of chronic HF patients with ICM or non-ischemic CM. This study identified sixteen miRNAs as differentially expressed between the two patient groups (miR-126, -508-5p, -34a, -210, -490-3p, -513-5p,

-517c, -518e, -589, -220c, -200a*, -186*, -7i*, -200b*, -595, -662) and conducted a survival analysis using the patients’ two-year follow up data. As a result, the levels of two of the differentially expressed miRNAs, miR-126 and -508-5p, were identified as independent prognostic factors of survival in both patient groups (P = 0.003; HR (hazard ratio): 0.19; 95% CI (confidence intervals): 0.06-0.58, and P = 0.002; HR: 2.292; 95% CI: 1.37-3.84 respectively). 132 This study brought to light two miRNAs that could be possibly

used as prognostic markers of the clinical outcome of CHF. In another study, the plasma concentrations of miR-126, -122 and -499 were measured in 33 congestive HF patients with ischemic heart disease and 17 asymptomtic controls. MiR-126 plasma levels were found to be decreased in HF patients, and negatively correlated with age, logBNP (B-type natriuretic peptide) and NYHA (New York Heart Association) class. 135 Interestingly, miR-126 Cilengitide levels increased with improvement of the NYHA class from IV to III, in ten of the HF patients investigated. This finding is in line with a putative correlation of miR-126 with HF clinical outcome suggested by Qiang et al in 2013. However, miR-126 downregulation has also been related to coronary artery disease. 136 Further investigation is required in order to assess if miR-126 downregulation is etiology-dependent or pertinent to HF development. Goren et al aimed to identify circulating miRNAs that can be used as markers for atrial fibrillation (AF), given that AF is associated with poor prognosis in HF patients.

Therefore, “encapsulated cell biodelivery” has been put forward a

Therefore, “encapsulated cell biodelivery” has been put forward as a novel clinical strategy for cell therapy in the CNS. Encapsulation was originally introduced to assist in allowing allogenic or xenogenic cell transplantation. It appears that semipermeable hollow fibers,29 as well as spherical polymeric microcapsules,30 protect cells transplanted into the brain from the immunological graft-versus-host response. As the capsules permit the free passage of nutrients, oxygen, and, indeed, smaller molecules, the cells are maintained within the capsules, and can produce and Inhibitors,research,lifescience,medical deliver therapeutic peptides to the brain.29, 30 Encapsulated cells have already been used for the therapy of diabetes

mellitus,31 amyotropic Inhibitors,research,lifescience,medical lateral sclerosis,32, 33 chronic pain,34 Huntington’s disease,35 and for the treatment of malignant brain tumors.36-38 Step 2: Preclinical studies Our group conducted a preclinical study testing the effect of encapsulated native MSCs and encapsulated glucagon -like pcptide-1 (GLP-1) transfected MSCs in experimental

traumatic brain injur}’ (controlled cortical impact- CCI).39 GLP-1 is an selleck chemical CHIR99021 endogenous insulin-stimulating peptide that is secreted from the gastrointestinal tract in response to food intake.40 GLP-1 receptors are also expressed throughout the mammalian brain.41 Stimulation of these receptors is associated with neuroprotective and Inhibitors,research,lifescience,medical neurotrophic activity.42-44 GLP-1 has been shown Inhibitors,research,lifescience,medical to improve learning and memory in GLP-1 receptor-deficient mice.45 The blood-to-brain delivery of native GLP-1 is, however, affected because GLP-1 rapidly degrades, with a plasma half-life of between 1 and 2 min.46 Hence, the cells were used as a ”bioreactor“ which constantly releases GLP-1, while simultaneously Inhibitors,research,lifescience,medical bypassing the blood-brain barrier. A human bone marrow-derived, mesenchymal stem cell line was used in this study. This cell line was immortalized by transduction with the human telomerase reverse transcriptase

(hTERT) gene.47 Following transfection with a plasmid vector encoding a GLP-1 fusion gene, the cells produced 8.7 kDa of dimeric GLP-1. The cells were alginate encapsulated Dacomitinib and stored in liquid nitrogen until used. Each capsule contained approximately 2300 cells. Animals were randomized into five groups: controls (no CCI); CCI-only; CCI + native human bone-marrow derived mesenchymal stem cells (hM’SC); CCI + GLP1 producing hMSC; and CCI + empty capsules. Twenty capsules were implanted into the right lateral ventricle immediately before CCI. Even though this technique does not mimic the clinical setting, it was necessary in order to ensure implantation of the encapsulated cells into the ventricle, since the standard stereotactic coordinates become invalid after the CCI due to contusion – related brain tissue shifting.

Among other important issues, this system can help surgeons to se

Among other important issues, this system can help surgeons to select the prosthesis that best fits patient’s anatomy among a wide range of sizes, or to design a custom-made one. To our knowledge, this is the first compound system trying to answer to all the technical issues involved in such an ambitious task.Figure 1 shows a schematic diagram of our system for pre-operative planning of knee replacement surgery. Various pieces of data are collected from different sources and processed. The first block is related to bone features: computed tomography (CT) scans and mechanical properties. CT volume elements (voxels) are classified into four different tissue classes (see Section 3.2.), in order to extract the geometry of cortical (external) and trabecular (internal) parts of the bones. Then, mechanical properties of the bone are estimated and mapped onto the CT scan (Section 3.3.). The second block encloses mechanical parameters and surface characteristics of the prosthesis, given by the manufacturer and plugged into the system (Section 4.). A detailed mathematical description of the bone-prosthesis contact is developed (Section 5.). Mechanical data of the tibia and femur, and of the prosthesis are used together with geometry for 3D meshing (Section 6.1.). The last block is related to simulation. 3D meshes and loading conditions are used for FEM simulation (Section 6.1.). A method to deal with uncertainties in the measurements has also been studied (Section 6.3.). The simulated stress results are mapped onto the geometry of the bones for analysis and learn more visualisation. Typical mechanical parameters for the specific clinical case can also be taken from statistical studies about similar cases in the literature, using patients’ info such as age, weight, and sex.Figure 1.Scheme of our system for pre-operative planning of knee replacement surgery.In the following sections we discuss each of these issues.3.?Bone ModellingWe model two aspects of bone structures for stress simulation: geometry and mechanical parameters of the bone. Geometry is extracted from CT scans of the patients’ knee joint using by means of an automatic classification algorithm. A statistical generative model is employed together with a Maximum A-posteriori Probability (MAP) classification rule [3]. The probability distributions used for classification are automatically learned from manually-annotated training scans. CT scans are used for two main reasons. First, acquiring CT data for planning is common clinical practice before knee replacement intervention. Second, CT scans give sufficiently accurate data for knee replacement surgery, as pointed out in [4].From a mechanical viewpoint, the bone is modelled as a three dimensional viscoelastic material. The two regions composing tibia and femur, cortical and trabecular, posses highly different properties that must be taken into account for an accurate stress simulation.