Trans-physeal anterior cruciate ligament reconstruction in adolescents.

PURPOSE: The aim of the study was to evaluate, in a group of adolescents, the onset of varus-valgus deviations in the sagittal plane after performing a trans-tibial trans-epiphyseal technique of ACL reconstruction with a follow-up of at least 2 years. METHODS: Seventy-one patients aged 12-15 years old (Tanner scale 3 and 4) have undergone ACL reconstruction with STG using arthroscopy. All patients were evaluated clinically using the visual analogue scale (VAS), the Lysholm score and the Tegner activity score at the time of surgery. All patients were reevaluated after a follow-up period of at least 2 years (T1) using the VAS, the Lysholm score, the Tegner activity score and radiographic studies in order to compare the operated limb with the healthy control limb. RESULTS: Valgus difference exceeding 2° in the knee axis between the operated limb and the healthy control limb was observed only in three patients (4.2%: 95% CI 0.88-11.86%). The average difference was <1° (0.3°, 95% CI 0.0-0.55). CONCLUSION: The trans-tibial trans-epiphyseal technique of ACL reconstruction, according to the results obtained, seems to be a valid alternative procedure, when performed by a skilled orthopaedic surgeon, offering an excellent safety profile and at the same time very good clinical results. LEVEL OF EVIDENCE: IV.

High accuracy in knee alignment and implant placement in unicompartmental medial knee replacement when using patient-specific instrumentation.

PURPOSE: The influence of patient-specific instrumentations on the accuracy of unicompartmental medial knee replacement remains unclear. The goal of this study was to examine the ability of patient-specific instrumentation to accurately reproduce postoperatively what the surgeon had planned preoperatively. METHODS: Twenty consecutive patients (20 knees) who suffered from isolated unicompartmental medial osteoarthritis of the knee and underwent medial knee replacement using newly introduced magnetic resonance imaging-based patient-specific instrumentation were assessed. This assessment recorded the following parameters: (1) the planned and the postoperative mechanical axis acquired through long-leg AP view radiographies; (2) the planned and the postoperative tibial slope acquired by means of standard AP and lateral view radiographies; and (3) the postoperative fit of the implanted components to the bone in coronal and sagittal planes. The hypothesis of the study was that there was no statistically significant difference between postoperative results and preoperatively planned values. RESULTS: The study showed that (1) the difference between the postoperative mechanical axis (mean 1.9° varus ± 1.2° SD) and the planned mechanical axis (mean 1.8° varus ± 1.2° SD) was not statistically significant; (2) the difference between the postoperative tibial slope (mean 5.2° ± 0.6° SD) and the planned tibial slope (mean 5.4° ± 0.6° SD) was statistically significant (p = 0.008); and (3) the postoperative component fit to bone in the coronal and sagittal planes was accurate in all cases; nevertheless, in one knee, all components were implanted one size smaller than preoperatively planned. Moreover, in two additional cases, one size thinner and one size thicker of the polyethylene insert were used. CONCLUSIONS: This study suggests that overall patient-specific instrumentation was highly accurate in reproducing postoperatively what the surgeon had planned preoperatively in terms of mechanical axis, tibial slope and component fit to bone. LEVEL OF EVIDENCE: IV.

Electrical conditioning of adipose-derived stem cells in a multi-chamber culture platform.

In tissue engineering, several factors play key roles in providing adequate stimuli for cells differentiation, in particular biochemical and physical stimuli, which try to mimic the physiological microenvironments. Since electrical stimuli are important in the developing heart, we have developed an easy-to-use, cost-effective cell culture platform, able to provide controlled electrical stimulation aimed at investigating the influence of the electric field in the stem cell differentiation process. This bioreactor consists of an electrical stimulator and 12 independent, petri-like culture chambers and a 3-D computational model was used to characterize the distribution and the intensity of the electric field generated in the cell culture volume. We explored the effects of monophasic and biphasic square wave pulse stimulation on a mouse adipose-derived stem cell line (m17.ASC) comparing cell viability, proliferation, protein, and gene expression. Both monophasic (8 V, 2 ms, 1 Hz) and biphasic (+4 V, 1 ms and -4 V, 1 ms; 1 Hz) stimulation were compatible with cell survival and proliferation. Biphasic stimulation induced the expression of Connexin 43, which was found to localize also at the cell membrane, which is its recognized functional mediating intercellular electrical coupling. Electrically stimulated cells showed an induced transcriptional profile more closely related to that of neonatal cadiomyocytes, particularly for biphasic stimulation. The developed platform thus allowed to set-up precise conditions to drive adult stem cells toward a myocardial phenotype solely by physical stimuli, in the absence of exogenously added expensive bioactive molecules, and can thus represent a valuable tool for translational applications for heart tissue engineering and regeneration.

Autologous collagen-induced chondrogenesis technique (ACIC) for the treatment of chondral lesions of the talus.

PURPOSE: Autologous collagen-induced chondrogenesis technique (ACIC) combines microfractures with the use of an injectable atelocollagen matrix that allows performing the whole cartilage repair treatment arthroscopically. The aim of this study was to evaluate the in vitro cytocompatibility of this biomaterial using human bone marrow mesenchymal stem cells and human chondrocytes. Moreover, the preliminary data of five patients affected by chondral lesion of the talus treated with the ACIC technique are shown. METHODS: Human bone marrow mesenchymal stem cells and human chondrocytes were seeded on solid and pre-solid atelocollagen scaffolds. Cell-scaffold constructs were cultured for 7 days and then prepared for histological analyses. Arthroscopic ACIC was performed in five patients affected by chondral lesions of the talus; they were clinically evaluated with AOFAS, VAS and Tegner score before and then after 6 months from surgery. RESULTS: In vitro results showed that both bone marrow mesenchymal stem cells and chondrocytes were able to efficiently colonize the whole construct, from the surface to the core, only when seeded on the pre-solid atelocollagen scaffold, but not on its solid form. No adverse events were observed in the patients treated with the ACIC technique; a significant improvement in VAS pain scale and in AOFAS score was found at 6 months follow up. CONCLUSION: Injectable atelocollagen can be considered a feasible scaffold for cartilage repair treatment, in particular if used in its pre-solid form. ACIC leads to good clinical results in the treatment for chondral lesions of the talus even if longer follow-up and a higher number of patients are necessary to confirm these data. LEVEL OF EVIDENCE: IV.

The role of vaginal Lactobacillus Rhamnosus (Normogin®) in preventing Bacterial Vaginosis in women with history of recurrences, undergoing surgical menopause: a prospective pilot study.

BACKGROUND: Bacterial vaginosis (BV), a poly-microbial clinical syndrome, is the most common cause of vaginal symptoms among women. The recurrence rate of BV is up to 30% after traditional antimicrobial therapy. Lactobacillus rhamnosus vaginal tablets have demonstrated to be a reliable topical effective and safe treatment to reduce the BV recurrence rate. AIM: to assess topical long-lasting (6 months) Lactobacillus rhamnosus effectiveness in decreasing recurrences in women with positive anamnesis of recurrent BV and concomitant hypo-estrogenism as consequence of surgical menopause. PATIENTS AND METHODS: A total of 22 consecutive patients affected by recurrent BV and treated for surgical menopause for benign pathology were enrolled. All women were treated with Lactobacillus rhamnosus vaginal tablets (Normogin(®)) according to the following protocol: 1 tablet/day for 6 days, than two tablets per week for 2 months and then one tablet once a week till 6 months. RESULTS: Of the 22 women enrolled only one has been lost after the first visit. A total of 21 cases were reported; 7 out of 21 had only one case of recurrence, while 2 out of 21 had two episodes of BV during the year successive to menopause. No side effects have been reported. CONCLUSIONS: Considering the low recurrence rate of BV during follow-up it seems that long-lasting treatment with vaginal tablets of Lactobacillus rhamnosus could reduce the BV recurrence also in women at high risk with positive history of pathology and undergoing surgical menopause with a safe profile. This study supports the use of vaginal Lactobacillus rhamnosus administration in high risk population without side effects.

SAMCEP Society consensus on the treatment of upper facial lines with botulinum neurotoxin type A: A tailored approach.

BACKGROUND: The safety and efficacy of botulinum neurotoxin type A (BoNTA) treatments are well established, but injection techniques, target muscles, and toxin doses continue to evolve, with each refinement producing improvements in treatment outcomes. The recommendations in this consensus move away from standard templates and illustrate how to tailor treatments to individual patterns and strengths of muscle activity, and patient preferences. METHODS: Seventeen experts in the fields of plastic surgery, dermatology, ophthalmology, otorhinolaryngology, and neurology convened in 2022 to develop consensus-based recommendations for the use of botulinum toxin A for the treatment of horizontal forehead lines, glabellar frown lines, and crow's feet lines that reflect current clinical practice. The focus was on how to tailor injections to individual patients to optimize treatment outcomes. RESULTS: For each upper face indication, consensus members describe how to perform a dynamic assessment to optimize the dose and injection technique for each patient. A tailored treatment protocol is presented for commonly observed patterns of dynamic lines. Units of Inco are defined and the precise location of injection points, illustrated with the use of anatomical images. CONCLUSION: This consensus provides up-to-date recommendations on the tailored treatment of upper facial lines based on the latest research and collective clinical experience of the expert injectors. Optimal outcomes require thorough patient evaluation, both at rest and during animation, using both visual and tactile cues; detailed understanding of facial muscular anatomy and how opposing muscles interact; and use of a BoNTA with high precision to target identified zones of excess muscle activity.

Preliminary baropodometric analysis of young soccer players while walking: geometric morphometrics and comparative evaluation.

AIM: The plantar support and its modifications are widely studied because of their bearing on posture. In particular, past studies have focused on the support modification during specific athletic tasks to highlight the eventual correlations between foot type and the most frequent sport injuries, due to intrinsic and extrinsic components that involve the structural and functional dynamics that act on the plantar vault during static and dynamic condition. These studies have been conducted by analyzing the morphological variation of the footprint during the performance. METHODS: In the present study the variation in shape of the baropodometrical footprint of young soccer players, has been analyzed using geometric morphometrics. This approach permits a quantification of the morphological variation of the subjects using Cartesian coordinates placed at specific points on the footprint outline, and to correlate them with physical variables. RESULTS: In the present study the young soccer players displayed a narrowing of the footprint due to a transversal variation on the isthmus, when compared to children of the same age who did not play soccer. These results suggest a physiological and biomechanical organization of the foot type in soccer due to the specific athletic tasks involved. CONCLUSION: As the foot type, in sport, is strictly associated to recurrent injuries, the result obtained in this study should be considered as indicative for future analysis. In fact, a clear and univocal knowledge of this phenomenon would be useful in the planning of a training protocol to reduce the incidence of sport related injuries.

Feasibility study of a mixed reality tool for real 3D visualization and planning of left atrial appendage occlusion.

In left atrial appendage occlusion (LAAO), pre-procedural imaging is pivotal to describe the highly variable LAA anatomy and to guide the operator in device sizing and interventional planning. Multiplanar reconstruction and 3D rendering are used for the interpretation of 3D CT datasets. However, this method of review of such imaging, which is mediated by 2D screens, may be limited due to the lack of true 3D visualization of the structures of interest; Mixed Reality (MxR) may further improve the CT-based pre-procedural planning by allowing for real-3D visualizations with holographic replicas of anatomical models. In this manuscript we present a novel software based on MxR and we evaluated its feasibility on different LAA morphologies. The morphological analysis of the holographic anatomical models was successfully applied for all the patients (n â€‹= â€‹4) independently from the morphology and it was performed in less than 10 minutes. Our findings suggest that with further developments MxR could have the potential to become a pivotal tool in LAA occlusion planning thanks to the real-3D perception, possibly leading to a more accurate and faster planning phase.

Subject-specific multiscale modeling of aortic valve biomechanics.

A Finite Element workflow for the multiscale analysis of the aortic valve biomechanics was developed and applied to three physiological anatomies with the aim of describing the aortic valve interstitial cells biomechanical milieu in physiological conditions, capturing the effect of subject-specific and leaflet-specific anatomical features from the organ down to the cell scale. A mixed approach was used to transfer organ-scale information down to the cell-scale. Displacement data from the organ model were used to impose kinematic boundary conditions to the tissue model, while stress data from the latter were used to impose loading boundary conditions to the cell level. Peak of radial leaflet strains was correlated with leaflet extent variability at the organ scale, while circumferential leaflet strains varied over a narrow range of values regardless of leaflet extent. The dependency of leaflet biomechanics on the leaflet-specific anatomy observed at the organ length-scale is reflected, and to some extent emphasized, into the results obtained at the lower length-scales. At the tissue length-scale, the peak diastolic circumferential and radial stresses computed in the fibrosa correlated with the leaflet surface area. At the cell length-scale, the difference between the strains in two main directions, and between the respective relationships with the specific leaflet anatomy, was even more evident; cell strains in the radial direction varied over a relatively wide range ([Formula: see text]) with a strong correlation with the organ length-scale radial strain ([Formula: see text]); conversely, circumferential cell strains spanned a very narrow range ([Formula: see text]) showing no correlation with the circumferential strain at the organ level ([Formula: see text]). Within the proposed simulation framework, being able to account for the actual anatomical features of the aortic valve leaflets allowed to gain insight into their effect on the structural mechanics of the leaflets at all length-scales, down to the cell scale.

Evaluation of GH-IGF-I axis in adult patients with coeliac disease.

The aim of this study was to evaluate GH/IGF-I axis and other pituitary functions in adult patients with coeliac disease. For this purpose, twenty-eight adult coeliac patients [20M, 8F:19-74 years; body mass index (BMI): 18.5-28 kg/m (2)] were recruited. Basal thyroid, adrenal and gonadal function, serum IGF-I and PRL, and routine parameters were evaluated. Dynamic GH secretion was carried out by GHRH plus arginine test. In 20 patients, antipituitary antibodies (APA) were also evaluated. Seven out of 28 patients, independently from disease onset and the gluten-free diet (GFD), showed an impaired GH secretion (25%). All were males, 2 with severe growth hormone deficiency (GHD) and 5 with partial GHD. In patients with GHD, as compared to coeliac patients with normal GH secretion, HOMA (2.1+/-1.2 vs. 0.9+/-0.4) and QUICKI (0.35+/-0.03 vs. 0.39+/-0.02) levels were significantly higher and lower, respectively, while IGF-I levels were slightly lower (17.7+/-3.7 vs. 24.7+/-6.3, p=NS). APA were negative in all 20 patients studied. In conclusion, a significant number of adult coeliac patients show an impaired GH secretion, this alteration being predominant in males and independent from disease onset and diet regimen. Given the absence of APAs, the cause of this pituitary dysfunction remains unclear even if a previous autoimmune involvement in some cases cannot be excluded.

[Treatment of hyperandrogenism and hyperinsulinemia in PCOS patients with essential amino acids. A pilot clinical study]. / Trattamento dell'perandrogenismo e dell'perinsulinemia con aminoacidi essenziali in pazienti affette da sindrome dell'ovaio policistico. Uno studio pilota.

AIM: Women with polycystic ovary syndrome (PCOS) report frequently hyperinsulinemia. The aim of this study was to evaluate the effects of 16-weeks therapy with essential amino acids supplements on metabolic and clinical indices in PCOS. METHODS: For this study ten women with PCOS and fasting hyperinsulinemia were enrolled. The study comprised 16 weeks of therapy with oral essential amino acids (Aminopril, NAMED, Milan, Italy) administered 4 g twice per day. Body mass index, hirsutism score, serum levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, lipoprotein(a), serum adrenal and ovarian androgens, fasting glucose and insulin concentrations, T, DHEAS, gonadotropins, and sex hormone-binding globulin (SHBG), were assessed before and after treatment with essential amino acids. RESULTS: A significant decrease in fasting insulin, total T, luteneizing hormone and follicle-stimulating hormone was reported after amino acids therapy and increase in SHBG, leading to a decrease in the free T index. In addition, a significant reduction in hirsutism score was reported. No significant decrease in mean body mass index and in lipid pattern was reported. CONCLUSION: A decline of insulin after treatment with essential amino acids was observed in women with PCOS as well as total and bioavailable T, leading to significant improvement of clinical symptoms of hyperandrogenism.

Does the Ventrica magnetic vascular positioner (MVP) for coronary artery bypass grafting significantly alter local fluid dynamics? A numeric study.

OBJECTIVE: Automatic devices have been recently introduced to make the anastomosis procedure quick and efficient when creating a coronary bypass on the beating heart. However, the implantation of these devices could modify the graft configuration, consistently affecting the hemodynamics usually found in the traditional anastomosis. As local fluid dynamics could play a significant role in the onset of vessel wall pathologies, in this article a computational approach was designed to investigate flow patterns in the presence of the Ventrica magnetic vascular positioner (Ventrica MVP) device. METHODS: A model of standard hand-sewn anastomosis and of automated magnetic anastomosis were constructed, and the finite volume method was used to simulate in silico realistic graft hemodynamics. Synthetic analytical descriptors -- i.e., time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and helical flow index (HFI) -- were calculated and compared for quantitative assessment of the anastomosis geometry hemodynamic performance. RESULTS: In this case study, the same most critical region was identified for the 2 models as the one with the lowest TAWSS and the highest OSI (TAWSS=0.229, OSI=0.255 for the hand-sewn anastomosis; TAWSS=0.297, OSI=0.171 for the Ventrica MVP(R)). However, the shape of the Ventrica MVP does not induce more critical wall shear stresses, oscillating flow and damped helicity in the graft fluid dynamics, as compared with conventional anastomosis. CONCLUSIONS: We found that the use of the Ventrica MVP for the case study under investigation was not associated with more critical fluid dynamics than with conventional hand-sewn anastomosis. Thereby, the device could facilitate beating heart and minimally invasive coronary artery bypass grafting without increasing local hemodynamic-related risks of failure.

Two fluid-structure approaches for 3D simulation of St. Jude Medical bileaflet valve opening.

This paper deals with the three-dimensional (3D) numerical simulation of the opening transient for a bileaflet mechanical heart valve (St. Jude Medical Hemodynamic Plus, 27 mm characteristic size). The discussion concerns two different types of ""partitioned"" fluid-structure models, with weak and strong coupling. Both approaches are based on a moving deforming mesh method as implemented in the CFD commercial software Fluent (Fluent Inc., USA), and both yielded dynamically consistent results from a quantitative viewpoint. There is a slight improvement (peak relative difference <1%) of the numerical solution (angles vs. time) when using the strong instead of the weak coupling model. This is of utmost importance when the considerable reduction of the computational costs for the weak scheme (about 60% less) is taken into account. However, the strong coupling model provides a more consistent physical description of the interaction when looking at small-scale features like stress close to geometrical singularities. In the experiments, the differences both in terms of time-to-peak delay (15% of the opening time) and in terms of underestimation of the peak velocity (8%) seemed due to defects in the fluid inertia assessment, which depends on initial and boundary data.

Towards the improved quantification of in vivo abnormal wall shear stresses in BAV-affected patients from 4D-flow imaging: Benchmarking and application to real data.

Bicuspid aortic valve (BAV), i.e. the fusion of two aortic valve cusps, is the most frequent congenital cardiac malformation. Its progression is often characterized by accelerated leaflet calcification and aortic wall dilation. These processes are likely enhanced by altered biomechanical stimuli, including fluid-dynamic wall shear stresses (WSS) acting on both the aortic wall and the aortic valve. Several studies have proposed the exploitation of 4D-flow magnetic resonance imaging sequences to characterize abnormal in vivo WSS in BAV-affected patients, to support prognosis and timing of intervention. However, current methods fail to quantify WSS peak values. On this basis, we developed two new methods for the improved quantification of in vivo WSS acting on the aortic wall based on 4D-flow data. We tested both methods separately and in combination on synthetic datasets obtained by two computational fluid-dynamics (CFD) models of the aorta with healthy and bicuspid aortic valve. Tests highlighted the need for data spatial resolution at least comparable to current clinical guidelines, the low sensitivity of the methods to data noise, and their capability, when used jointly, to compute more realistic peak WSS values as compared to state-of-the-art methods. The integrated application of the two methods on the real 4D-flow data from a preliminary cohort of three healthy volunteers and three BAV-affected patients confirmed these indications. In particular, quantified WSS peak values were one order of magnitude higher than those reported in previous 4D-flow studies, and much closer to those computed by highly time- and space-resolved CFD simulations.

A novel approach to the quantification of aortic root in vivo structural mechanics.

Understanding aortic root in vivo biomechanics can help in elucidating key mechanisms involved in aortic root pathologies and in the outcome of their surgical treatment. Numerical models can provide useful quantitative information. For this to be reliable, detailed aortic root anatomy should be captured. Also, since the aortic root is never unloaded throughout the cardiac cycle, the modeled geometry should be consistent with the in vivo loads acting on it. Achieving such consistency is still a challenge, which was tackled only by few numerical studies. Here we propose and describe in detail a new approach to the finite element modeling of aortic root in vivo structural mechanics. Our approach exploits the anatomical information yielded by magnetic resonance imaging by reconstructing the 3-dimensional end-diastolic geometry of the aortic root and makes the reconstructed geometry consistent with end-diastolic loading conditions through the estimation of the corresponding prestresses field. We implemented our approach through a semiautomated modeling pipeline, and we applied it to quantify aortic root biomechanics in 4 healthy participants. Computed results highlighted that including prestresses into the model allowed for pressurizing the aortic root to the end-diastolic pressure while matching the image-based ground truth data. Aortic root dynamics, tissues strains, and stresses computed at relevant time points through the cardiac cycle were consistent with a broad set of data from previous computational and in vivo studies, strongly suggesting the potential of the method. Also, results highlighted the major role played by the anatomy in driving aortic root biomechanics.

Mass-spring models for the simulation of mitral valve function: Looking for a trade-off between reliability and time-efficiency.

Patient-specific finite element (FE) models can assess the impact of mitral valve (MV) repair on the complex MV anatomy and function. However, FE excessive time requirements hamper their use for surgical planning; mass-spring models (MSMs) represent a more approximate approach but can provide almost real-time simulations. On this basis, we implemented MSMs of three healthy MVs from cardiac magnetic resonance (cMR) imaging to simulate the systolic MV closure, including the in vivo papillary muscles and annular kinematics, and the anisotropic and non-linear mechanical response of MV tissues. To test MSM reliability we compared the systolic peak configurations computed by MSMs and FE: mismatches by less than twice the in-plane cMR image resolution were detected over 75% of the leaflets' surface, independently of the MSM mesh refinement and of the specific MV anatomy. Data on MSMs time-efficiency and data from the comparison of MSMs vs. FE models suggest that MSM could represent a suitable trade-off between almost real-time simulations and reliability when computing MV systolic configuration, with the potential to be used in a clinical setting either as a support to the decisional process or as a virtual training tool.

Multi-scale analysis of the toraymyxin adsorption cartridge. Part II: computational fluid-dynamic study.

Extracorporeal endotoxin removal by means of the Toraymyxin device is based on the ability of polymyxin B to bind endotoxins with a high specificity. The endotoxins/polymyxin molecular interactions were computationally analyzed in a parallel work (Part I). In this paper we investigate with a multi-scale approach the phenomena involving blood and plasma fluid dynamics inside the device. The macro- and mesoscale phenomena were studied by means of 3D models using computational fluid dynamics. The flow behavior in the sorbent material was focused, modeling the sorbent as a homogeneous porous medium at the macroscale level, or accounting for the realistic geometry of its knitted fibers at the mesoscale level. A microscale model was then developed to analyze the behavior of endotoxin molecules subjected to the competition of flow drag and molecular attraction by fiber-grafted polymyxin B. The macroscale results showed that a very regular flow field develops in the sorbent, furthermore supplying the peak velocity to be input in the lower-scale model. The mesoscale analysis yielded the realistic range for wall shear stresses (WSSs) acting on fiber walls. With WSS values in the entire range, the results of the microscale analysis demonstrated that the capability of polymyxin B to capture endotoxin molecules from the flow extends at distances one order of magnitude greater than the characteristic distance of the stable intermolecular bond. We conclude that the use of an integrated, multi-scale analysis allows for a comprehensive understanding of the complex mechanisms involved in endotoxin sorption phenomena with immobilized polymyxin B.

Multi-scale analysis of the toraymyxin adsorption cartridge. Part I: molecular interaction of polymyxin B with endotoxins.

Endotoxins or lipopolysaccharides are the main constituents of the outer leaflet of Gram-negative bacteria membrane and play a central role in the pathogenesis of the septic shock. Polymyxin B has both antibacterial and antiendotoxin capability; indeed it is able to destroy the bacterial outer membrane and bind endotoxin neutralizing its toxic effects. Cartridges containing polymyxin B-immobilized fibers (Toraymyxin PMX-F, Toray Industries, Japan) are used in extracorporeal hemoperfusion to remove circulating endotoxin. The aim of this study is the characterization of the polymyxin B-endotoxin system at the molecular level, thus providing quantitative evaluation of the binding forces exerted in the molecular complex. Polymyxin B was interfaced with five molecular models of lipopolysaccharides differing in their structure and molecular mechanics simulations were performed at different intermolecular distances aimed at calculating the interaction energies of the complex. Binding forces were calculated by fitting interaction energies data. Results show that in the short range the polymyxin B-endotoxin complex is mediated by hydrophobic forces and in the long range the complex is driven by ionic forces only. From a mechanical standpoint, polymyxin B-endotoxin complex is characterized by maximum binding forces ranging between 1.39 nN to 3.79 nN. The knowledge of the binding force behavior at different intermolecular distances allows further investigations at higher scale level (Part II).

Interferon-induced depression: prevalence and management.

BACKGROUND: Interferon-induced depression ranges from 0 to 50%. Interferon schedule and a history of psychiatric illnesses are not enough to predict who will develop symptoms and who will not. AIMS: To assess the prevalence of depression during interferon therapy; to test whether Minnesota Multiphasic Personality Inventory is useful in clinical practice for the early identification of patients at risk of depression; whether and how the depression can be cured. PATIENTS: One hundred and eighty-five patients treated with interferon and ribavirin for chronic hepatitis C. METHODS: Before therapy, all patients underwent a Minnesota Multiphasic Personality Inventory and a clinical examination, specifically for the identification of depressive symptoms. RESULTS: Thirty-one patients developed a psychiatric disorder, 11 of them requiring treatment with anti-depressant drugs. Among the 18 patients with Minnesota Multiphasic Personality Inventory positive tests, 16 developed a psychiatric disorder, 8 of them a severe disorder (sensitivity of 0.58; 0.73 for severe disorders). Among the 154 who did not develop psychiatric side effects, 152 had a negative Minnesota Multiphasic Personality Inventory (specificity: 0.99). Severe psychiatric disorders were successfully treated with anti-depressant drugs. CONCLUSIONS: Psychiatric side effects are easy to see during interferon therapy. A psychiatric evaluation should be considered on all patients before treatment. If depression develops, it should be treated aggressively, and selective serotonin re-uptake inhibitors are the anti-depressants of choice.

Influence of the aortic valve leaflets on the fluid-dynamics in aorta in presence of a normally functioning bicuspid valve.

In this work, we consider the blood fluid-dynamics in the ascending aorta in presence of a normally functioning bicuspid aortic valve (BAV). In particular, we perform an unsteady finite element study in real geometries with physiological velocity boundary conditions at the inlet to assess the effect of the inclusion of the leaflets on the fluid-dynamic abnormalities characterizing BAV cases. To this aim, we perform a comparison in two geometries (a dilated and a non-dilated ones) among three scenarios which are built up for each geometry: BAV without leaflets, BAV with leaflets, and tricuspid case with leaflets. For each case, we compute four indices quantifying flow asymmetry, reversal flows, helical patterns, and wall shear stresses. Our results show that the inclusion of the leaflets increases the fluid-dynamics abnormalities, especially for the non-dilated configuration, which presents a greater increment of the indices. In particular, we observe that the values of the time-averaged wall shear stress and of the systolic jet asymmetry increase by approximatively 100 and 40%, respectively, when considering the leaflets.