Artificial intelligence-based radiomics on computed tomography of lumbar spine in subjects with fragility vertebral fractures.

PURPOSE: There is emerging evidence that radiomics analyses can improve detection of skeletal fragility. In this cross-sectional study, we evaluated radiomics features (RFs) on computed tomography (CT) images of the lumbar spine in subjects with or without fragility vertebral fractures (VFs). METHODS: Two-hundred-forty consecutive individuals (mean age 60.4 ± 15.4, 130 males) were evaluated by radiomics analyses on opportunistic lumbar spine CT. VFs were diagnosed in 58 subjects by morphometric approach on CT or XR-ray spine (D4-L4) images. DXA measurement of bone mineral density (BMD) was performed on 17 subjects with VFs. RESULTS: Twenty RFs were used to develop the machine learning model reaching 0.839 and 0.789 of AUROC in the train and test datasets, respectively. After correction for age, VFs were significantly associated with RFs obtained from non-fractured vertebrae indicating altered trabecular microarchitecture, such as low-gray level zone emphasis (LGLZE) [odds ratio (OR) 1.675, 95% confidence interval (CI) 1.215-2.310], gray level non-uniformity (GLN) (OR 1.403, 95% CI 1.023-1.924) and neighboring gray-tone difference matrix (NGTDM) contrast (OR 0.692, 95% CI 0.493-0.971). Noteworthy, no significant differences in LGLZE (p = 0.94), GLN (p = 0.40) and NGDTM contrast (p = 0.54) were found between fractured subjects with BMD T score < - 2.5 SD and those in whom VFs developed in absence of densitometric diagnosis of osteoporosis. CONCLUSIONS: Artificial intelligence-based analyses on spine CT images identified RFs associated with fragility VFs. Future studies are needed to test the predictive value of RFs on opportunistic CT scans in identifying subjects with primary and secondary osteoporosis at high risk of fracture.

Psychobiological evidence of the stress resilience fostering properties of a cosmetic routine.

Everyday life psychosocial stressors contribute to poor health and disease vulnerabilty. Means alternative to pharmacotherapy that are able to foster stress resilience are more and more under the magnifying glass of biomedical research. The aim of this study was to test stress resilience fostering properties of the self-administration of a cosmetic product enriched with essential oils. On day 0, fourty women, 25-50 years old, self-administered both the enriched cosmetic product (ECP) and a placebo one (PCP). Then, women were randomized for daily self-administration (from day 1 to 28) of either ECP (n = 20) or PCP (n = 20). On day 29, subjects underwent a psychosocial stress test (PST). Autonomic (heart rate and its variability) and neuroendocrine (salivary cortisol) parameters were assessed both on day 0 and 29. All subjects filled a number of psychological questionnaires in order to quantify anxiety, perceived stress, and mood profile, and were videorecorded during PST for non-verbal behavior evaluation. A single application of ECP produced an acute potentiation of cardiac parasympathetic modulation, which was not observed when placebo was used. Prolonged self-administration of ECP induced: (i) a dampening of the cortisol rise produced by PST, (ii) a reduction of state anxiety, (iii) a favorable change in mood profile, and (iv) a reduction of non-verbal behavior patterns that signal anxiety, motivational conflict and avoidance. In conclusion, this study suggests that the self-administration of a cosmetic cream enriched with essential oils should be considered as a stress resilience fostering strategy due to its favorable physiological, neuroendocrine and psychological effects.

Dietary cyanidin 3-glucoside from purple corn ameliorates doxorubicin-induced cardiotoxicity in mice.

BACKGROUND AND AIMS: Anthracyclines are effective anticancer drugs that have improved prognosis of hundred thousand cancer patients worldwide and are currently the most common chemotherapeutic agents used for the treatment of blood, breast, ovarian and lung cancers. However, their use is limited because of a cumulative dose-dependent and irreversible cardiotoxicity that can cause progressive cardiomyopathy and congestive heart failure. Aim of the present study was to determine the cardioprotective activity of a dietary source of cyanidin 3-glucoside (C3G), such as purple corn, against doxorubicin (DOX)-induced cardiotoxicity in mice. METHODS AND RESULTS: In vitro studies on murine HL-1 cardiomyocytes showed that pretreatment with both pure C3G and purple corn extract improved survival upon DOX treatment. However, C3G and purple corn extract did not affect the cytotoxic effect of DOX on human cancer cell lines. We then validated in vivo the protective role of a C3G-enriched diet against DOX-induced cardiotoxicity by comparing the effect of dietary consumption of corn isogenic lines with high levels of anthocyanins (purple corn - Red diet - RD) or without anthocyanins (yellow corn - Yellow diet - YD) incorporated in standard rodent diets. Results showed that mice fed RD survived longer than mice fed YD upon injection of a toxic amount of DOX. In addition, ultrastructural analysis of hearts from mice fed RD showed reduced histopathological alterations. CONCLUSION: Dietary intake of C3G from purple corn protects mice against DOX-induced cardiotoxicity.

The role of copper in the thermal conductivity of thermoelectric oxychalcogenides: do lone pairs matter?

Understanding the underlying mechanisms that suppress thermal conduction in solids is of paramount importance for the targeted design of materials for thermal management and thermoelectric energy conversion applications. Bismuth copper oxychalcogenides, BiOCuQ (Q = Se, Te), are highly crystalline thermoelectric materials with an unusually low lattice thermal conductivity of ∼0.5 Wm(-1) K(-1), a value normally found in amorphous materials. Here we unveil the origin of the unusual thermal transport properties of these phases. First principles calculations of the vibrational properties combined with analysis of in-situ neutron diffraction data, demonstrate that weak bonding of copper atoms within the structure leads to an unexpected vibrational mode at low frequencies, which is likely to be a major contributor to the low thermal conductivity of these materials. In addition, we show that anharmonicity and the large Grüneisen parameter in these oxychalcogenides are mainly related to the low frequency copper vibrations, rather than to the Bi(3+) lone pairs.

Isthmocele in a retroflexed uterus: a report of an unrecognized case.

The term "isthmocele" refers to a niche on the anterior wall of the uterine isthmus or of the cervical canal at the site of a previous cesarean delivery scar. Such anatomic defect can cause many gynecologic sequelae that only recently have being identified and described. Hysteroscopy is commonly considered the gold standard for the diagnosis and also for the treatment, at least in the case of defects of small size. The authors described the case of a 37-year-old woman who underwent a cesarean section (CS) seven years before, with a long lasting history of menstrual irregularities, and pelvic pain increasing during menstruation at the hypogastric level. Magnetic resonance imaging (MRI) showed an exceptionally large isthmocele on the anterior wall of a retroflexed uterus which was otherwise misinterpreted as the uterine cavity filled with menstrual blood during a previous hysteroscopy (HSC). Although exceptional, this case highlights the possibility that a large sized isthmocele in a retroflexed uterus could be misinterpreted as the uterine cavity filled by menstrual blood at HSC. In this case MRI definitely clarified the diagnosis.

MRI in the assessment of prolapsed pedunculated submucous leiomyomas: two case reports.

Uterine leiomyomas are the most common benign gynecological tumors affecting 20-30% of women in reproductive age. Despite their benignity, in some cases several symptoms may require surgical intervention. Submucosal leiomyomas are less frequent (5-10%), but are usually symptomatic. Approximately 2.5% of the myomas are pedunculated and can protrude in the cervical canal. Symptomatic leiomyomas can be treated either by hysterectomy or myomectomy, and these procedures can be performed with several techniques. Whenever possible, hysteroscopic myomectomy is better because it has many advantages, as it also preserves future fertility. Two interesting cases of prolapsed pedunculated submucous leiomyomas are reported in order to prove that magnetic resonance imaging (MRI) is essential to choose the most appropriate treatment and to perform an adequate presurgical planning, which must be based on an overall assessment of the leiomyoma's characteristics (number, location, size and presence or absence of a stalk) and the patient's characteristics.

Thoughts and concerns of patients at hospital discharge after lumbar spine surgery. A qualitative study.

PURPOSE: The increased rate of surgical interventions point to the necessity to investigate the patient's experience from a biopsychosocial perspective. The aim of this study was to investigate the thoughts and concerns of patients undergoing spinal surgery for lumbar degenerative disease at the time of their discharge from hospital. METHODS: Semi-structured interviews were conducted with 28 patients. The questions investigated possible concerns associated to discharging them home. A content analysis was performed by a multidisciplinary group to identify the main themes that emerged from the interviews. RESULTS: The patients were satisfied with the surgeons' preoperative explanations and description of expected prognosis. However, they were disappointed with the lack of information at hospital discharge, in particular regarding practical and behavioral recommendations. The patients expressed clear concerns about being left alone to deal with possible complications or difficulties they may encounter when returning home. CONCLUSION: This study underlined the patients' need for a comprehensive psychological guidance and possibly a person of reference during the post-operative process. Discussing discharge with the patient was emphasized as an important issue to improve patients' compliance to the recovery process itself. Putting these elements into practice should help spine surgeons to manage better hospital discharge.IMPLICATIONS FOR REHABILITATIONA comprehensive discussion with the patient at the time of hospital discharge is clearly stressed as an important issue to improve patients' adherence to the recovery process.The patients complained of a lack of information when returning home, in particular regarding practical and behavioral recommendations.The patients expressed clear concerns about possible complications or difficulties they may encounter when returning home and they expressed their need to know whom they can contact for help if needed.A better understanding of the thoughts and concerns of patients undergoing spinal surgery at the time of their discharge from hospital should help spine surgeons to improve the management of hospital discharge and the post-operative recovery.

Pharmacokinetic and pharmacodynamic study of three products of epoetin alfa as single subcutaneous dose in healthy volunteers.

Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980s and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40 000 IU of Eprex/Erypo® and Hemax® PFS. This clinical trial was conceived following an open-label, randomized, three-way three-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. To analyze similarity between Hemax® PFS and the innovator product, Eprex®, area under the curve (AUC) and Cmax of both products have been compared. The 90% CI lower limit for the geometric mean ratios was higher than 80% for any comparisons, and the 90% CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. The comparison between Hemax® PFS and Eprex® resulted in similar 90% CI for Cmax , AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent, and elimination (with an elimination half-life close to 25-30 h for each formulation).

A prenylated flavanone from Dalea elegans inhibits rhodamine 6 G efflux and reverses fluconazole-resistance in Candida albicans.

In previous studies, 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12-99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12-99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12-99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.

Early versus delayed laparoscopic cholecystectomy for acute cholecystitis.

AIM: Laparoscopic cholecystectomy, currently the gold standard treatment for cholelithiasis, has been extended to treating acute cholecystitis as well. However, operation timing remains controversial. The aim of this retrospective study was to compare our data on the timing of surgery for early and delayed laparoscopic cholecystectomy for acute cholecystitis. METHODS: From January 1, 2006 to December 31, 2010, 508 laparoscopic cholecystectomy procedures were performed, 149 of which for acute cholecystitis: 122 operations were defined as early (performed within 72 hours of symptom onset) and 27 as delayed (72 hours to 9 days from symptom onset). RESULTS: There were no statistically significant differences in operating time, conversion or complications rates between early and delayed procedures. The total length of hospital stay was longer for patients who had undergone a delayed procedure. The success rates were similar irrespective of the surgeon's level of experience. CONCLUSION: Patients operated on for acute cholelithiasis between 72 hours and up to 9 days after symptom onset may benefit similarly as from an earlier operation. Delayed laparoscopic cholecystectomy for acute cholelithiasis is a feasible and safe procedure that compares favorably with early laparoscopic cholecystectomy.

Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly.

OBJECTIVES: In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls. PATIENTS: Eighteen patients with active acromegaly and 18 controls were studied. MEASUREMENTS: Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry. RESULTS: After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 +/- 17 vs. 141 +/- 30% per ml h, respectively; P < 0.05). Endothelin-1 levels evidenced an increase in the patients' group (0.9 +/- 0.2 vs. 0.7 +/- 0.2 ng/l, respectively; P < 0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42 and 0.44, respectively; P < 0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 +/- 59 vs. 246 +/- 48 arbitrary units, respectively; P < 0.05). CONCLUSIONS: Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.

Efficacy of treatment with percutaneous vertebroplasty and kyphoplasty for traumatic fracture of thoracolumbar junction.

AIM: The aim of this paper was to assess the efficacy of a minimally invasive treatment with percutaneous vertebroplasty and kyphoplasty for traumatic fracture of thoracolumbar junction. Treatment of stable traumatic vertebral fractures of the thoracolumbar junction without neurological deficit is still controversy. Conservative treatment, characterized by discomfort and limitation in patient mobility, was progressively replaced by minimally invasive techniques such as percutaneous vertebroplasty and kyphoplasty. METHODS: Between January 2003 and August 2005, 34 patients suffering from 42 thoracolumbar fractures were treated at Neurosurgical Department of Istituto Galeazzi (Milan). The treatment selected (vertebroplasty versus kyphoplasty), depended on age of patients, timing and type of fracture. Results were clinically assessed by Visual Analogue Score (VAS) and Oswestry Disability Index. RESULTS: Mean preoperative VAS was 8.32 (range 5-10). Percutaneous vertebroplasty was performed in 25 cases (73.5%); while 9 patients were treated by kyphoplasty (27.5%); 27 patients showed a single level and 7 multilevel of the fractures. No complications occurred (infection, neurological deficit, embolic events) after treatment. At the early follow-up 91.7% of the patients achieved a good pain control already after 24 hours. Pain relief and disability, analyzed by VAS and Oswestry Disability Index, showed a good results at late follow-up time. CONCLUSIONS: Percutaneous vertebroplasty and kyphoplasty are two safe and effective techniques for treatment of thoracolumbar traumatic fractures and allow a good pain-control and return to normal working activity and social life.

Molecular MR imaging for the evaluation of the effect of dynamic stabilization on lumbar intervertebral discs.

The dynamic stabilization of lumbar spine is a non-fusion stabilization system that unloads the disc without the complete loss of motion at the treated motion segment. Clinical outcomes are promising but still not definitive, and the long-term effect on instrumented and adjacent levels is still a matter of discussion. Several experiments have been devised in order to gain a better understanding of the effect of the device on the intervertebral disc. One of the hypotheses was that while instrumented levels are partially relieved from loading, adjacent levels suffer from the increased stress. But this has not been proved yet. The aim of this study was to investigate the long-term effect of dynamic stabilization in vivo, through the quantification of glycosaminoglycans (GAG) concentration within instrumented and adjacent levels by means of the delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) protocol. Ten patients with low back pain, unresponsive to conservative treatment and scheduled for Dynesys implantation at one to three lumbar spine levels, underwent the dGEMRIC protocol to quantify GAG concentration before and 6 months after surgery. Each patient was also evaluated with visual analog scale (VAS), Oswestry, Prolo, Modic and Pfirrmann scales, both at pre-surgery and at follow-up. Six months after implantation, VAS, Prolo and Oswestry scales had improved in all patients. Pfirrmann scale could not detect any change, while dGEMRIC data already showed a general improvement in the instrumented levels: GAG was increased in 61% of the instrumented levels, while 68% of the non-instrumented levels showed a decrease in GAG, mainly in the posterior disc portion. In particular, seriously GAG-depleted discs seemed to have the greatest benefit from the Dynesys implantation, whereas less degenerated discs underwent a GAG depletion. dGEMRIC was able to visualize changes in both instrumented and non-instrumented levels. Our results suggest that the dynamic stabilization of lumbar spine is able to stop and partially reverse the disc degeneration, especially in seriously degenerated discs, while incrementing the stress on the adjacent levels, where it induces a matrix suffering and an early degeneration.

Parametric FE mesh generation: application to the cervical spine.

A voxel-based reconstruction algorithm, targeted at the generation of finite element (FE) meshes of structures with schematic geometry, is presented. The algorithm is able to generate three dimensional fully hexahedral FE meshes of structures composed of volumes with a schematic geometry. In order to be meshed, each volume must be described in terms of a set of surfaces which enclose the volume. Due to its schematic nature, the method allows the generation of fully parameterized FE models, thus it facilitates the investigation of the mechanical relevance of geometrical parameters by speeding up the mesh generation process. The algorithm was employed in the automatic construction of an FE model of the C3-C7 spinal segment with schematic geometry, made up exclusively of hexahedral elements. Non-linear simulations were carried out in different loading conditions: flexion- extension, lateral bending and axial rotation. The results were compared to data retrieved from the literature in order to ensure the validity of the model. Moment-rotation curves for each loading condition were determined. The range of motion was obtained for each spinal unit and loading condition. Both principal and coupled rotations were determined in lateral bending and axial rotation, for each spinal unit. The intradiscal pressure was also computed in the nucleus pulposus, for all the intervertebral levels. Geometrical parameterization of the models offers potential for the biomechanical investigation of pathologic conditions and surgical procedures, such as spinal fusion and disc arthroplasty, even on a patient-specific basis.

Cardiometabolic Changes in Different Gonadal Female States Caused by Mild Hyperuricemia and Exposure to a High-Fructose Diet.

BACKGROUND: The objective of this study is to observe if mild hyperuricemia and a high-fructose diet influence the cardiovascular and metabolic systems in hypogonadic female Wistar rats compared to normogonadic female rats. METHODS: Fifty-six (56) adult female Wistar rats were used in the present work. Animals were divided into two groups: normogonadic (NGN) and hypogonadic (HGN). These groups were also divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Lipid profile, glycemia, uric acid, and creatinine determinations were assessed. Cardiovascular changes were evaluated by measuring blood pressure, myocyte volume, fibrosis, and intima-media aortic thickness. RESULTS: HGN rats had higher levels of total cholesterol (TC) (p < 0.01) and noHDLc (p < 0.01), in addition to higher levels of uric acid (p < 0.05). The OA group significantly increased myocyte volume (p < 0.0001) and the percentage of fibrosis as well as the group receiving FOA (p < 0.001) in both gonadal conditions, being greater in the HGN group. Hypogonadic animals presented a worse lipid profile. CONCLUSION: Mild hyperuricemia produces hypertension together with changes in the cardiac hypertrophy, fibrosis, and increased thickness of the intima media in hypogonadic rats fed high-fructose diet.

237 ACoA aneurysms clipped or embolized. Outcomes measurement using the De Santis-CESE assessment tool.

AIM: The aim of this retrospective study was to demonstrate the difference in patient outcomes after treatment for bleeding endocranial aneurysms when evaluated with methods based on different assessment criteria. METHODS: The outcome of 237 patients, 141 of which were operated on for anterior communicating artery aneurysm and 96 embolized, was assessed by a new method developed by De Santis. The patients operated on were assessed by the Glasgow Outcome Scale (GOS) and Rank Disability Scale (RDS) and the results of the latter were compared with the new method, the De Santis-CESE (Clinical Emotional Social Evaluation) method, which consists of a clinical evaluation and a numeric scoring system based on seven standard points. Comparison between the three methods showed significantly different outcomes. Patients who underwent surgical operation showed changes in character and behaviour, whereas the others showed cognitive, emotional and sexual habit changes. CONCLUSION: Compared with the GOS and RDS instruments, the CESE method showed significant differences in patient outcome assessment, particularly regarding best outcomes. These differences may be due to the greater sensitivity of the CESE method over the other two scales. Furthermore, surgical patients seemed to achieve a better outcome than endovascular patients. The authors intend to conduct a prospective study to test the results obtained in this retrospective study.

Biomechanics of the C5-C6 spinal unit before and after placement of a disc prosthesis.

The study consists of a biomechanical comparison between the intact C5-C6 spinal segment and the same segment implanted with the Bryan artificial disc prosthesis (Medtronic Ltd., Memphis, TN, USA), by the use of the finite element (FE) method. Our target is the prediction of the influence of prosthesis placement on the resulting mechanics of the C5-C6 spine unit. A FE model of the intact C5-C6 segment was built, employing realistic models of the vertebrae, disc and ligaments. Simulations were conducted imposing a compression preload combined to a flexion/extension moment, a pure lateral bending moment and a pure torsion moment, and the calculated results were compared to data from literature. The model was then modified to include the Bryan cervical disc prosthesis, and the simulations were repeated. The location of the instantaneous center of rotation (ICR) of C5 with respect to C6 throughout flexion/extension was calculated in both models. In general, the moment-rotation curves obtained from the disc prosthesis-implanted model were comparable to the curves obtained from the intact model, except for a slightly greater stiffness induced by the artificial disc. The position of the calculated ICRs was rather stable throughout flexion-extension and was generally confined to a small area, qualitatively matching the corresponding physiological region, in both models. These results imply that the Bryan disc prosthesis allows to correctly reproduce a physiological flexion/extension at the implanted level. The results of this study have quantified aspects that may assist in optimizing cervical disc replacement primarily from a biomechanical point of view.

Multibody modeling of the cervical spine in the simulation of flexion-extension after disc arthroplasty.

This paper presents a three-dimensional (3D) multibody model of the cervical spine implanted with an artificial disc. The model was used to predict prosthesis placement influence on the resulting cervical kinematics in a series of patients. The vertebral tract modeled was the C2-C7, and the vertebral geometries were reconstructed from computed tomography (CT) images. The model was used to simulate the flexion-extension motion of the cervical spine in 10 patients implanted with the Prestige commercial disc prosthesis at a single level. For each patient, a geometrical model of the prosthesis was scaled and included in the multibody model to match the size and positioning of the actual prosthesis, as assessed on post-operative radiographs. Simulations of complete flexion-extension were carried out for each patient, and the main parameters relevant to the motion of the vertebral bodies were calculated and compared to data measured from dynamic post-operative radiographs. At the implanted level, the simulated ranges of motion generally agreed with the measured ones, with an average deviation <2 degrees. In addition, the simulated relative angles between vertebral bodies agreed with the measured ones, with minor average differ-ences of 1.2, 1.8 and 2.1 degrees in full flexion, neutral alignment and full extension, respectively. The cervical kinematics after prosthesis placement was influenced both by the design of the artificial joint and by surgical positioning. Therefore, the model presented can be used both to support pre-operative planning for disc arthroplasty and in the optimization of new prostheses design.

In vivo effect of snake phospholipase A2 (crotoxin+cardiotoxin) on serum IL-1alpha, TNF-alpha and IL-1ra level in humans.

VRCTC-310-Onco (crotoxin, a secretory phospholipase A2+cardiotoxin) is under development as an anti-neoplastic agent. Pro-inflammatory cytokines TNF-alpha and interleukin 1 alpha (IL-1alpha) and anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) were measured with commercial ELISA kits in sera corresponding to 23 cycles with doses between 0.0025 and 0.023 microg/kg body weight, obtained during the phase I trial of VRCTC-310-Onco. Neither serum TNF-alpha nor IL-1alpha did change significantly after VRCTC-310-Onco. Basal IL-1ra was 794 +/- 97 pg/ml, by 3 h it was similar, 651 +/- 99 pg/ml and at 24 h p.i. it increased to 1197 +/- 122 pg/ml (P<0.001). The increase was dose-dependent. The addition of dexamethasone (required to reduce pain with the highest doses) inhibited IL-1alpha and enhanced the induction of IL-1ra by VRCTC-310-Onco. Summing up, in vivo, in humans, in the dose range tested, VRCTC-310-Onco induces IL-1ra, and does not consistently modify IL-1alpha or TNF-alpha serum levels.