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Amino acid modified graphene nanosheets adsorb emerging contaminants from tap water outperforming unmodified precursors and activated carbon for carbamazepine, bisphenol A and benzophenone 4. Structure–adsorption relationships are unraveled.

In this work, we exploit Langmuir adsorption isotherms to compare the performance of different materials (adsorbents) in removing contaminants (adsorbates) from water.

Graphene nanosheets have outstanding adsorption efficiency toward organic molecules but the potential as sorbent for water purification is strongly limited by the tedious recovery of the nanosheets after the treatment, which can cause secondary contaminations. Here, we demonstrate that graphene oxide (GO) and reduced GO (rGO) nanosheets aggregation in tap water, enabling their separation by dead-end microfiltration (MF) on commercial polymeric hollow fiber modules. No evidence of GO/rGO contamination was found in microfiltered water and chemical potability of treated water was confirmed by standard protocols. Moreover, GO/rGO can be recovered (by inverting the filtration modality from IN-OUT to OUT-IN), washed and reused, this allowing the regeneration and reuse of both graphene nanosheets and the filtration module. The procedure (called here GO + MF) was optimized on tap water spiked with ofloxacin (OFLOX) or methylene blue (MB), as reference. The optimized procedure was then applied both with GO and rGO to the removal of a mixture of perfluoroalkyl substances (PFASs) from tap water at mu g/L levels, the highest concentration found in water resources abstracted for water consumption. We demonstrate that rGO + MF procedure allows to remove 138 mu g/g of total PFASs in only 30 min, i.e. an efficiency 3-5 times higher than granular activated carbon (43 mu g/g) used in real potabilization plants for PFASs removal.

Hepatocellular carcinoma is the third most common cause of cancer-related death according to the International Agency for Research on Cancer. Dihydroartemisinin (DHA), an antimalarial drug, has been reported to exhibit anticancer activity but with a short half-life. We synthesized a series of bile acid–dihydroartemisinin hybrids to improve its stability and anticancer activity and demonstrated that an ursodeoxycholic–DHA (UDC-DHA) hybrid was 10-fold more potent than DHA against HepG2 hepatocellular carcinoma cells. The objectives of this study were to evaluate the anticancer activity and investigate the molecular mechanisms of UDCMe-Z-DHA, a hybrid of ursodeoxycholic acid methyl ester and DHA via a triazole linkage. We found that UDCMe-Z-DHA was even more potent than UDC-DHA in HepG2 cells with IC50 of 1 μM. Time course experiments and stability in medium determined by cell viability assay as well as HPLC-MS/MS analysis revealed that UDCMe-Z-DHA was more stable than DHA, which in part accounted for the increased anticancer activity. Mechanistic studies revealed that UDCMe-Z-DHA caused G0/G1 arrest and induced reactive oxygen species (ROS), mitochondrial membrane potential loss and autophagy, which may in turn lead to apoptosis. Compared to DHA, UDCMe-Z-DHA displayed much lower cytotoxicity toward normal cells. Thus, UDCMe-Z-DHA may be a potential drug candidate for hepatocellular carcinoma.

Commercial hollow fiber filters for micro- and ultrafiltration are based on size exclusion and do not allow the removal of small molecules such as antibiotics. Here, we demonstrate that a graphene oxide (GO) layer can be firmly immobilized either inside or outside polyethersulfone-polyvinylpyrrolidone hollow fiber (Versatile PES®, hereafter PES) modules and that the resulting core-shell fibers inherits the microfiltration ability of the pristine PES fibers and the adsorption selectivity of GO. GO nanosheets were deposited on the fiber surface by filtration of a GO suspension through a PES cartridge (cut-off 0.1-0.2 μm), then fixed by thermal annealing at 80 °C, rendering the GO coating stably fixed and unsoluble. The filtration cut-off, retention selectivity and efficiency of the resulting inner and outer modified hollow fibers (HF-GO) were tested by performing filtration on water and bovine plasma spiked with bovine serum albumin (BSA, 66 kDa, ≈15 nm size), monodisperse polystyrene nanoparticles (52 nm and 303 nm sizes), with two quinolonic antibiotics (ciprofloxacin and ofloxacin) and rhodamine B (RhB). These tests showed that the microfiltration capability of PES was retained by HF-GO, and in addition the GO coating can capture the molecular contaminants while letting through BSA and smaller polystyrene nanoparticles. Combined XRD, molecular modelling and adsorption experiments show that the separation mechanism does not rely only on physical size exclusion, but involves intercalation of solute molecules between the GO layers.

Background: Desmoplastic Fibroma (DF) of bone is a locally aggressive and infrequent benign neoplasm. Recently was described a role of vascular endothelial growth factor in the interstitial fibrotic processes. Case presentation: A 13-year-old female presented with pain, swelling and limitation of movements in right forearm. An osteolytic lesion at the distal end of the right radius was shown, with pathologic concentration of Technetium 99 and slight enhancement of soft tissue lesion employing computerized axial tomography. The surgical biopsy showed nodular formations of hyalinized collagen fibers arranged in thick bands with few well-differentiated interstitial fibroblasts / myofibroblasts, focally expressing VEGF-A. Conclusion: The intramedullary neoplastic proliferation is limited by the cortical bone, provoking compression of the intratumorally micro-vessels, favoring both, the extracellular matrix and VEGF-A synthesis. Future research should include therapeutic intervention with anti-CD117 and anti-VEGF-A drugs, with the aim of limiting tumor growth, facilitating the complete surgical excision of the neoplasm. Keywords: desmoplastic fibroma; vascular endothelial growth factor; hyalinization; neoplasm progression.

The Eddy current flowmeter sensor plays an important part in the instrumentation of the future sodium fast reactors, which will allow when located above the core to detect plugging (partial or total) of a subassembly and when located on the primary pump to measure core pressure drop and core flowrate. This article describes the predesign phase of a mockup for Eddy current flowmeter tests and qualifications under sodium conditions for the detection of a partial or full plugging of a fuel subassembly. These tests will be the first of their kind, as the Eddy current flowmeter had never been qualified at nominal conditions of a reactor core outlet (sodium temperature, velocity, and output flow).

Las poroqueratosis son un grupo heterogéneo de trastornos de la queratinización epidérmica, de presentación infrecuente. Se caracterizan clínicamente por pápulas hiperqueratósicas que confluyen formando placas anulares con un centro atrófico y bordes sobreelevados. Hay seis variantes clínicas. El examen histopatológico evidencia la característica laminilla cornoide. Se presenta el caso de una niña de 2 años con diagnóstico de poroqueratosis de Mibelli y respuesta parcial al tratamiento tópico con tretinoínaal 0,025%, que actualmente continúa en seguimiento clínico.

BACKGROUND: The anterior cruciate ligament is the primary structural restraint to tibial anterior shear force. The anterior force occurring at the knee during landing contributes to anterior cruciate ligament injury risk, but it cannot be directly measured experimentally. PURPOSE: The objective of this study was to develop electromyography-informed musculoskeletal simulations of the drop vertical jump motor task and assess the contribution of knee muscle forces to tibial anterior shear force. STUDY DESIGN: cross-sectional study. METHODS: Musculoskeletal simulations were used to estimate the muscle forces of thirteen female athletes performing a drop vertical jump using an electromyography-informed method. Muscle activation and knee loads that resulted from these simulations were compared to the results obtained with the more common approach of minimization of muscle effort (optimization-based method). Quadriceps-hamstrings and quadriceps-gastrocnemius co-contractions were progressively increased and their contribution to anterior shear force was quantified. RESULTS: The electromyography-informed method produced co-contraction indexes more consistent with electromyography data than the optimization-based method. The muscles that presented the largest contribution to peak anterior shear force were the gastrocnemii likely from their wrapping around the posterior aspect of the tibia. The quadriceps-hamstring co-contraction provided a protective effect on the ACL and reduced peak anterior shear force by 292 N with a co-contraction index increase of 25% from baseline (31%), whereas a quadriceps-gastrocnemius co-contraction index of 61% increased peak anterior shear force by 797 N compared to baseline (42%). CONCLUSION: An increase in gastrocnemius contraction, which might be required to protect the ankle from the impact with the ground, produced a large quadriceps-gastrocnemius co-activation, increasing peak anterior shear force. CLINICAL RELEVANCE: A better understanding of each muscle’s contribution to anterior shear force and, consequently, anterior cruciate ligament tension may inform subject-specific injury prevention programs and rehabilitation protocols.

The mechanism underlying non-contact anterior cruciate ligament (ACL) injury is multi-factorial and still an object of debate. Computational models, in combination with in vivo and cadaveric studies, can provide valuable insight into the contribution of the different factors involved. The goal of this study was to validate four knee finite element models (two males and two females) to kinematic and strain data collected in vitro with an impact-driven simulator and use them to assess how secondary external knee loads (knee abduction moment [KAM], anterior shear force, and internal rotation torque [ITR]) affect tibiofemoral contact forces and ACL force during impact. Four subject-specific knee models were developed from specimen computed tomography and magnetic resonance imaging. Patellofemoral and tibiofemoral ligament properties were calibrated to match experimentally measured kinematics and ligament strain. Average root mean square errors and correlations between experimental and model-predicted knee kinematics were below 1.5 mm and 2°, and above 0.75, respectively. Similar errors and correlations were obtained for ACL strain ( 2% and 0.9). Model-predicted ACL forces were highly correlated with the anterior component of the tibiofemoral contact force on the lateral plateau occurring during impact (r = 0.99), which was increased by larger KAM and ITR through the posterior tibial slope and a larger contact force on the lateral side. This study provides a better understanding of the mechanism through which secondary external knee loads increase ACL injury risk during landing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1730-1742, 2019.

Background: Anterior cruciate ligament (ACL) injury reduction training has focused on lower body strengthening and landing stabilization. In vitro studies have shown that quadriceps forces increase ACL strain, and hamstring forces decrease ACL strain. However, the magnitude of the effect of the quadriceps and hamstrings forces on ACL loading and its timing during in vivo landings remains unclear. Purpose: To investigate the effect and timing of knee muscle forces on ACL loading during landing. Study Design: Descriptive laboratory study. Methods: A total of 13 young female athletes performed drop vertical jump trials, and their movements were recorded with 3-dimensional motion capture. Lower limb joint motion and muscle forces were estimated with OpenSim and applied to a musculoskeletal finite element (FE) model to estimate ACL loading during landings. The FE simulations were performed with 5 different conditions that included/excluded kinematics, ground-reaction force (GRF), and muscle forces. Results: Simulation of landing kinematics without GRF or muscle forces yielded an estimated median ACL strain and force of 5.1% and 282.6 N. Addition of GRF to kinematic simulations increased ACL strain and force to 6.8% and 418.4 N ( P < .05). Addition of quadriceps force to kinematics + GRF simulations nonsignificantly increased ACL strain and force to 7.2% and 478.5 N. Addition of hamstrings force to kinematics + GRF simulations decreased ACL strain and force to 2.6% and 171.4 N ( P < .001). Addition of all muscles to kinematics + GRF simulations decreased ACL strain and force to 3.3% and 195.1 N ( P < .001). With hamstrings force, ACL loading decreased from initial contact (time of peak: 1-18 milliseconds) while ACL loading without hamstrings force peaked at 47 to 98 milliseconds after initial contact ( P = .024-.001). The knee flexion angle increased from 20.9° to 73.1° within 100 milliseconds after initial contact. Conclusion: Hamstrings activation had greater effect relative to GRF and quadriceps activation on ACL loading, which significantly decreased and regulated the magnitude and timing of ACL loading during in vivo landings. Clinical Relevance: Clinical training should focus on strategies that influence increased hamstrings activation during landing to reduce ACL loads.

Defect-rich graphene oxide (dGO) was used as sorbent for organic contaminants of emerging concern in tap water, including drugs and dyes, and the performance compared to those of lower-defects graphene types. The role of holes and carbonyl- carboxylic groups on graphene nanosheets surface on the adsorption mechanism and efficiency was investigated. dGO showed enhanced adsorption capacity toward two fluoroquinolone antibiotics (ofloxacin, OFLOX, and ciprofloxacin, CIPRO) in tap water with a maximum capacity of 650 mg/g, compared to 204 mg/g for Hummers derived commercial GO (hGO) and 125 mg/g for less defected Brodie derived GO (bGO) for OFLOX. The role of defects on the selective adsorption of OFLOX was also modelled by MD simulations, highlighting a mechanism mainly driven by the shape complementarity between the graphene holes and the molecules. Adsorption isotherms revealed different adsorption model for dGO, with a Langmuir fitting for dGO and BET fitting for all the other investigated samples. The maximum adsorption capacity of dGO for OFLOX was about six times higher than that of Granular Activated Carbon (95 mg/g), the industrial adsorption standard technology. Finally, it was also demonstrated that dGO can be recovered from treated water by ultrafiltration, this preventing secondary contamination risks and enabling safe use of graphene nanosheets for water purification.

The study aimed to assess the effectiveness of an educational intervention promoting adherence to healthy diet and physical activity.Before-after interventional study.Participants were healthy volunteers, 18-70 y old, from Bologna. They followed a training course consisting of seven meetings and signed a contract to comply with the promoted habits, verified through questionnaires at the engagement phase (T0), three months later (T1) and one year later (T2).One hundred, fifty-three subjects were involved, 75.8% were evaluated at T1 and 41.2% at T2. More than 80% of the subjects involved at T1 achieved an improvement of planned goals. Moreover, 77% of T1 compliants retained healthy eating and physical activity at T2.The proposed pathway of empowerment positively affected nutrition and promotion of physical activity at 3 months after the intervention (T1) and were maintained even after a year. The results appear to be promising for primary prevention across the spectrum of a healthy lifestyle educational approach.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults and accounts for 85–90% of all primary liver cancer. Based on the estimation by the International Agency for Research on Cancer in 2018, liver cancer is the fourth leading cause of cancer death globally. Dihydroartemisinin (DHA), the main active metabolite of artemisinin derivatives, is a well-known drug for the treatment of malaria. Previous studies have demonstrated that DHA exhibits antitumor effects toward a variety of human cancers and has a potential for repurposing as an anticancer drug. However, its short half-life is a concern and may limit the application in cancer therapy. We have reported that UDC-DHA, a hybrid of bile acid ursodeoxycholic acid (UDCA) and DHA, is ∼12 times more potent than DHA against a HCC cell line HepG2. In this study, we found that UDC-DHA was also effective against another HCC cell line Huh-7 with an IC50 of 2.16 μM, which was 18.5-fold better than DHA with an IC50 of 39.96 μM. UDC-DHA was much more potent than the combination of DHA and UDCA at 1:1 molar ratio, suggesting that the covalent linkage rather than a synergism between UDCA and DHA is critical for enhancing DHA potency in HepG2 cells. Importantly, UDC-DHA was much less toxic to normal cells than DHA. UDC-DHA induced G0/G1 arrest and apoptosis. Both DHA and UDC-DHA significantly elevated cellular reactive oxygen species generation but with different magnitude and timing in HepG2 cells; whereas only DHA but not UDC-DHA induced reactive oxygen species in Huh-7 cells. Depolarization of mitochondrial membrane potential was detected in both HepG2 and Huh-7 cells and may contribute to the anticancer effect of DHA and UDC-DHA. Furthermore, UDC-DHA was much more stable than DHA based on activity assays and high performance liquid chromatography-MS/MS analysis. In conclusion, UDC-DHA and DHA may exert anticancer actions via similar mechanisms but a much lower concentration of UDC-DHA was required, which could be attributed to a better stability of UDC-DHA. Thus, UDC-DHA could be a better drug candidate than DHA against HCC and further investigation is warranted.

Concurrent multiscale simulation strategies are required in computational biomechanics to study the interdependence between body scales. However, detailed finite element models rarely include muscle recruitment due to the computational burden of both the finite element method and the optimization strategies widely used to estimate muscle forces. The aim of this study was twofold: first, to develop a computationally efficient muscle force prediction strategy based on proportional-integral-derivative (PID) controllers to track gait and chair rise experimental joint motion with a finite element musculoskeletal model of the lower limb, including a deformable knee representation with 12 degrees of freedom; and, second, to demonstrate that the inclusion of joint-level deformability affects muscle force estimation by using two different knee models and comparing muscle forces between the two solutions. The PID control strategy tracked experimental hip, knee, and ankle flexion/extension with root mean square errors below 1°, and estimated muscle, contact and ligament forces in good agreement with previous results and electromyography signals. Differences up to 11% and 20% in the vasti and biceps femoris forces, respectively, were observed between the two knee models, which might be attributed to a combination of differing joint contact geometry, ligament behavior, joint kinematics, and muscle moment arms. The tracking strategy developed in this study addressed the inevitable tradeoff between computational cost and model detail in musculoskeletal simulations and can be used with finite element musculoskeletal models to efficiently estimate the interdependence between muscle forces and tissue deformation.

Patellar complications after total knee replacement (TKR), such as maltracking, fracture, wear, and loosening, can lead to implant failure and revision surgery. However, few in vitro patellofemoral durability tests for the implanted joint have been developed. Existing standards for patellofemoral loading profiles (ISO 14243–5, draft) are generic (not implant-specific) and do not include patient variability. The goal of this study was to derive implant-specific loading profiles to simulate a motor task that reaches high knee flexion and include patient variability. In vivo data, including motion capture and stereo-radiographic images at the knee, were collected for eleven rotating platform TKR patients performing a single-leg lunge activity. Quadriceps forces during the activity were estimated for each patient from marker data and ground forces with a musculoskeletal model. Patellofemoral contact forces were estimated with patient-specific finite element models of the implanted knees. Stereo-radiography patellofemoral kinematics and estimated contact loads were combined to derive seven loading profiles that span the observed inter-patient variability. The loading profiles were experimentally evaluated in a 6-degree-of-freedom testing machine and worst-case loading profiles were identified. The two profiles that generated the highest stresses in the patellar button (43% and 46% of the volume surpassed yield stress, respectively) included the largest internal (4.4°) and external (13.0°) patellar rotation, and greater medio/lateral contact forces (up to 915 N). The same profiles were also tested in a finite element model of the experimental simulator, which was able to adequately replicate location and magnitude of the peak deformations measured in the prostheses after the experiment. The kinematic and loading profiles developed in this study simulated a high-demand motor task and incorporated inter-patient variability, capturing worst-case patellofemoral configurations, and can be utilized for pre-clinical testing of new patellar designs.

Introduction Musculoskeletal modeling allows insight into the interaction of muscle force and knee joint kinematics that cannot be measured in the laboratory. However, musculoskeletal models of the lower extremity commonly use simplified representations of the knee that may limit analyses of the interaction between muscle forces and joint kinematics. The goal of this research was to demonstrate how muscle forces alter knee kinematics and consequently muscle moment arms and joint torque in a musculoskeletal model of the lower limb that includes a deformable representation of the knee. Methods Two musculoskeletal models of the lower limb including specimen-specific articular geometries and ligament deformability at the knee were built in a finite element framework and calibrated to match mean isometric torque data collected from 12 healthy subjects. Muscle moment arms were compared between simulations of passive knee flexion and maximum isometric knee extension and flexion. In addition, isometric torque results were compared with predictions using simplified knee models in which the deformability of the knee was removed and the kinematics at the joint were prescribed for all degrees of freedom. Results Peak isometric torque estimated with a deformable knee representation occurred between 45° and 60° in extension, and 45° in flexion. The maximum isometric flexion torques generated by the models with deformable ligaments were 14.6% and 17.9% larger than those generated by the models with prescribed kinematics; by contrast, the maximum isometric extension torques generated by the models were similar. The change in hamstrings moment arms during isometric flexion was greater than that of the quadriceps during isometric extension (a mean RMS difference of 9.8 mm compared to 2.9 mm, respectively). Discussion The large changes in the moment arms of the hamstrings, when activated in a model with deformable ligaments, resulted in changes to flexion torque. When simulating human motion, the inclusion of a deformable joint in a multi-scale musculoskeletal finite element model of the lower limb may preserve the realistic interaction of muscle force with knee kinematics and torque.

Many emerging contaminants pass through conventional wastewater treatment plants, contaminating surface and drinking water. The implementation of advanced oxidation processes in existing plants for emerging contaminant remediation is one of the challenges for the enhancement of water quality in the industrialised countries. This paper reports on the production of a TiO2 nano-layer on quartz wool in a relevant amount, its characterisation by X-ray diffraction and scanning electron microscopy, and its use as a photocatalyst under ultraviolet radiation for the simultaneous mineralisation of five emerging organic contaminants (benzophenone-3, benzophenone-4, carbamazepine, diclofenac, and triton X-100) dissolved in deionised water and tap water. This treatment was compared with direct ultraviolet photolysis and with photocatalytic degradation on commercial TiO2 micropearls. The disappearance of every pollutant was measured by high performance liquid chromatography and mineralisation was assessed by the determination of total organic carbon. After 4 hours of treatment with the TiO2 nano-coated quartz wool, the mineralisation exceeds 90% in deionised water and is about 70% in tap water. This catalyst was reused for seven cycles without significant efficiency loss.

Acquired tracheal stenosis is a very infrequent lesion in the pediatric age group and may be due to diverse causes, being post-intubation stenosis and stenosis secondary to tracheostomy the most common ones. The management of acquired tracheal stenosis remains controversial. Endoscopic treatment provides immediate relief of symptoms but it is associated with a high recurrence rate, and the use of endoluminal prostheses can increase the length of the stricture complicating future surgery. Conversely, good long-term results have been documented with tracheal resection and primary anastomosis. We describe our experience with tracheal resection followed by end-to-end anastomosis for the treatment of post-intubation tracheal stenosis in 8 patients.

The initial fixation of cementless tibial trays after total knee arthroplasty is crucial to bony ingrowth onto the porous surface of the implants, as micromotion magnitudes exceeding 150 μm may inhibit bone formations and limit fixation. Experimental measurement of the interface micromotions is still very challenging. Thus, previous studies investigated micromotions at the bone-tray interface via finite element methods, but few performed direct validation via in vitro cadaveric testing under physiological loading conditions. Additionally, previous models were validated by solely considering relative displacements of the marker couples placed around the tray-bone interface. In this paper, we present an experimental-computational validation framework for investigating micromotions at the tray-bone interface under physiological conditions. Three cadaveric specimens were implanted with cementless rotating-platform implants and tested under gait, deep knee bending, and stair descent loads. Corresponding subject-specific finite element models were developed and used to predict the marker (tray-bone) relative displacements and tibial surface displacements. Experimental measurements were used to validate model estimations. Subsequent sensitivity analyses were performed on implantation and friction parameters to represent model uncertainties. The models appropriately differentiated between locations, activities, and specimens. The average root-mean-square (RMS) differences and correlations between measured marker relative displacements and predictions from the ‘best-matching’ models were 13.1 μm and 0.86. RMS differences and correlations between measured surface displacements and predictions were 78.9 μm and 0.84. Full-field interface micromotions were investigated and compared with predicted marker relative displacements. The marker relative displacements underestimated the actual interface micromotions. Initial tray-bone alignment in anterior-posterior, flexion-extension, and varus-valgus degrees of freedom have a considerable impact on the interface micromotions. The validated cadaveric models can be further used for pre-clinical assessments of new TKR tray design. The outcomes of the sensitivity analyses provide further insights into reducing interface micromotions via clinical techniques.

The study aimed to offer a path of empowerment to promote adherence to healthy diets and physical activity for cancer prevention,according to the recommendations of the World Cancer Research Fund (2007): 5 servings per day of fruit / vegetables, protective food (EVO, green tea, cruciferous, turmeric, dried fruit), practicing at least 30 minutes of moderate physical activity. Participants were volunteers between 18 - 70 years old divided in groups of 25/30 people. They followed a course of 7 theoretical and practical meetings (lifestyles, resilience and cooking workshops) and they signed a contract to comply with the promoted habits, which were verified through questionnaires administered during the engagement phase (T0), three months after the beginning of the course (T1) and one year after (T2). Six editions (2014-2017) were made for a total of 153 subjects involved (75% women, average age 54 years old). Of these, 116 eligible subjects (76%) were also evaluated at T1 and 63 volunteers (41.7%) at T2. With respect to the dropped out rate, 24% of the subjects left the study prior T1, while 45% of volunteers left it prior T2. The established goal (40% expected target) was accomplished and excided the expectation, since more than 80% of the subjects involved at T1 achieved an improvement in healthy diet (increased consumption of vegetables and fruit, daily consumption of at least one food with antioxidant action) and physical activity (at least 30 minutes a day). Furthermore the 77% of T1 compliants (50% expected goal) retained healthy eating and healthy motor behaviors even after a year (T2). The proposed path of empowerment positively affected nutrition and promotion of physical activity at 3 months after the intervention (T1) and were maintained even after a year. The latter result was partly scale down by a high drop out. The path of empowerment, appropriately adapted, can complete the diagnostic therapeutic pathways for breast cancer and colon cancer survivors. Key messages People are easier involved in empowerment paths aimed at fighting a single disease, for example cancer, but good results can be achieved simultaneously for all non-communicable diseases. Motivational communication for healthy eating, physical activity and stress prevention must become an integral part of the therapeutic diagnostic pathways of cancers and non-communicable diseases.

Background: A recently developed mechanical impact simulator induced an anterior cruciate ligament (ACL) rupture via the application of a combination of inverse dynamics–based knee abduction moment (KAM), anterior tibial shear force (ATS), and internal tibial rotation moment with impulsive compression in a cohort of cadaveric limbs. However, there remains an opportunity to further define the interaction of internal forces and moments at the knee and their respective influence on injury events. Purpose: To identify the influence of internal knee loads on an ACL injury event using a cadaveric impact simulator. Study Design: Controlled laboratory study. Methods: Drop-landing simulations were performed and analyzed on 30 fresh-frozen cadaveric knees with a validated mechanical impact simulator. Internal forces and moments at the knee joint center were calculated using data from a 6-axis load cell recorded on the femur during testing. Kinetic data from a total of 1083 trials that included 30 ACL injury trials were used as inputs for principal component (PC) analysis to identify the most critical features of loading waveforms. Logistic regression analysis with a stepwise selection was used to select the PCs that predicted an ACL injury. Injurious waveforms were reconstructed with selected PCs in logistic regression analysis. Results: A total of 3 PCs were selected in logistic regression analysis that developed a significant model ( P < .001). The external loading of KAM was highly correlated with PC1 (ρ < –0.8; P < .001), which explained the majority (>69%) of the injurious waveforms reconstructed with the 3 selected PCs. The injurious waveforms demonstrated a larger internal knee adduction moment and lateral tibial force. After the ACL was ruptured, decreased posterior tibial force was observed in injury trials. Conclusion: These findings give us a better understanding of ACL injury mechanisms using 6-axis kinetics from an in vitro simulator. An ACL rupture was correlated with an internal knee adduction moment (external KAM) and was augmented by ATS and lateral tibial force induced by an impact, which distorted the ACL insertion orientation. Clinical Relevance: The ACL injury mechanism explained in this study may help target injury prevention programs to decrease injurious knee loading (KAM, ATS, and lateral tibial force) during landing tasks.

Acquired tracheal stenosis is a very infrequent lesion in the pediatric age group and may be due to diverse causes, being post-intubation stenosis and stenosis secondary to tracheostomy the most common ones. The management of acquired tracheal stenosis remains controversial. Endoscopic treatment provides immediate relief of symptoms but it is associated with a high recurrence rate, and the use of endoluminal prostheses can increase the length of the stricture complicating future surgery. Conversely, good long-term results have been documented with tracheal resection and primary anastomosis. We describe our experience with tracheal resection followed by end-to-end anastomosis for the treatment of post-intubation tracheal stenosis in 8 patients.La estenosis traqueal adquirida es muy poco frecuente en la edad pediátrica y puede responder a múltiples causas; la estenosis posintubación y la secundaria a traqueotomía son las más comunes. El manejo de la estenosis traqueal adquirida sigue siendo controvertido. El tratamiento endoscópico proporciona el alivio inmediato de los síntomas, pero se asocia a una alta tasa de recurrencia, y el uso de prótesis endoluminales puede incrementar la longitud de la estenosis y complicar una cirugía futura. Por el contrario, se han documentado buenos resultados a largo plazo con la resección traqueal con anastomosis primaria. Se describe nuestra experiencia con la resección traqueal con anastomosis término-terminal para el tratamiento de la estenosis traqueal posintubación en 8 pacientes.

The click azide = alkyne 1,3-dipolar cycloaddition (click chemistry) has become the approach of choice for bioconjugations in medicinal chemistry, providing facile reaction conditions amenable to both small and biological molecules. Many nucleoside analogs are known for their marked impact in cancer therapy and for the treatment of virus diseases and new targeted oligonucleotides have been developed for different purposes. The click chemistry allowing the tolerated union between units with a wide diversity of functional groups represents a robust means of designing new hybrid compounds with an extraordinary diversity of applications. This review provides an overview of the most recent works related to the use of click chemistry methodology in the field of nucleosides, nucleotides and nucleic acids for pharmacological applications.

Background: Frontal plane trunk lean with a side-to-side difference in lower extremity kinematics during landing increases unilateral knee abduction moment and consequently anterior cruciate ligament (ACL) injury risk. However, the biomechanical features of landing with higher ACL loading are still unknown. Validated musculoskeletal modeling offers the potential to quantify ACL strain and force during a landing task. Purpose: To investigate ACL loading during a landing and assess the association between ACL loading and biomechanical factors of individual landing strategies. Study Design: Descriptive laboratory study. Methods: Thirteen young female athletes performed drop vertical jump trials, and their movements were recorded with 3-dimensional motion capture. Electromyography-informed optimization was performed to estimate lower limb muscle forces with an OpenSim musculoskeletal model. A whole-body musculoskeletal finite element model was developed. The joint motion and muscle forces obtained from the OpenSim simulations were applied to the musculoskeletal finite element model to estimate ACL loading during participants’ simulated landings with physiologic knee mechanics. Kinematic, muscle force, and ground-reaction force waveforms associated with high ACL strain trials were reconstructed via principal component analysis and logistic regression analysis, which were used to predict trials with high ACL strain. Results: The median (interquartile range) values of peak ACL strain and force during the drop vertical jump were 3.3% (–1.9% to 5.1%) and 195.1 N (53.9 to 336.9 N), respectively. Four principal components significantly predicted high ACL strain trials, with 100% sensitivity, 78% specificity, and an area of 0.91 under the receiver operating characteristic curve ( P < .001). High ACL strain trials were associated with (1) knee motions that included larger knee abduction, internal tibial rotation, and anterior tibial translation and (2) motion that included greater vertical and lateral ground-reaction forces, lower gluteus medius force, larger lateral pelvic tilt, and increased hip adduction. Conclusion: ACL loads were higher with a pivot-shift mechanism during a simulated landing with asymmetry in the frontal plane. Specifically, knee abduction can create compression on the posterior slope of the lateral tibial plateau, which induces anterior tibial translation and internal tibial rotation. Clinical Relevance: Athletes are encouraged to perform interventional and preventive training to improve symmetry during landing.

The advantages of a treatment modality that combines two or more therapeutic agents in cancer therapy encourages the study of hybrid functional compounds for pharmacological applications. In light of this, we reviewed recent works on hybrid molecules based on bile acids. Due to their biological properties, as well as their different chemical/biochemical reactive moieties, bile acids can be considered very interesting starting molecules for conjugation with natural or synthetic bioactive molecules.

Objective: A resolution passed by the government of the Brazilian state of São Paulo established a protocol for requesting free COPD medications, including tiotropium bromide, creating regional authorization centers to evaluate and approve such requests, given the high cost of those medications. Our objective was to analyze the requests received by an authorization center that serves cities in the greater metropolitan area of (the city of) São Paulo between 2011 and 2016. Methods: Data regarding the authorization, return, or rejection of the requests were compiled and analyzed in order to explain those outcomes. Subsequently, the clinical and functional data related to the patients were evaluated. Results: A total of 7,762 requests for dispensing COPD medication were analyzed. Requests related to male patients predominated. Among the corresponding patients, the mean age was 66 years, 12% were smokers, 88% had frequent exacerbations, and 84% had severe/very severe dyspnea. The mean FEV1 was 37.2% of the predicted value. The total number of requests decreased by 24.5% from 2012 to 2013 and was lowest in 2015. Most (65%) of the requests were accepted. The main reasons for the rejection/return of a request were a post-bronchodilator FEV1/FVC ratio > 0.7, a post-bronchodilator FEV1 > 50% of the predicted value, and failure to provide information regarding previous use of a long-acting β2 agonist. During the study period, the total number of requests returned/rejected decreased slightly, and there was improvement in the quality of the data included on the forms. Conclusions: Here, we have identified the characteristics of the requests for COPD medications and of the corresponding patients per region served by the authorization center analyzed, thus contributing to the improvement of local public health care measures.

Prospective knee abduction moments measured during the drop vertical jump task identify those at increased risk for anterior cruciate ligament injury. The purpose of this study was to determine which muscle forces and frontal plane biomechanical features contribute to large knee abduction moments. Thirteen young female athletes performed three drop vertical jump trials. Subject-specific musculoskeletal models and electromyography-informed simulations were developed to calculate the frontal plane biomechanics and lower limb muscle forces. The relationships between knee abduction moment and frontal plane biomechanics were examined. Knee abduction moment was positively correlated to vertical (R = 0.522, P < 0.001) and lateral ground reaction forces (R = 0.395, P = 0.016), hip adduction angle (R = 0.358, P < 0.023) and lateral pelvic tilt (R = 0.311, P = 0.061). A multiple regression showed that knee abduction moment was predicted by reduced gluteus medius force and increased vertical and lateral ground reaction forces (P < 0.001, R2 = 0.640). Hip adduction is indicative of lateral pelvic shift during landing. The coupled hip adduction and lateral pelvic tilt were associated to the increased vertical and lateral ground reaction forces, propagating into higher knee abduction moments. These biomechanical features are associated with ACL injury and may be limited in a landing with increased activation of the gluteus medius. Targeted neuromuscular training to control the frontal pelvic and hip motion may help to avoid injurious ground reaction forces and consequent knee abduction moment and ACL injury risk.

A pilomatrixoma is a benign skin tumor common in children, which develops from the matrix cells of hair follicles. It presents as a nodule or tumor of approximately 0.5-3 cm in size, with calcium-like consistency, faceted edges, and blue erythematous overlying skin. Sometimes, the skin may atrophy and look like a blister or even extrude calcium. Diagnosis is suspected based on the typical clinical presentation and supplementary imaging tests. The definite diagnosis is made according to histological findings. Surgical removal is the treatment of choice. Here we describe the epidemiological and clinical data, supplementary tests, and surgical techniques in relation to 149 pilomatrixomas resected in 137 patients treated at the Departments of Dermatology of two children's hospitals: Dr. Pedro de Elizalde and Prof. Dr. Juan P. Garrahan.El pilomatrixoma es un tumor benigno cutáneo, de frecuente aparición en los niños, que se origina en las células de la matriz del folículo piloso. Se presenta como un nódulo o tumor, aproximadamente, de 0,5 a 3 cm de tamaño, de consistencia cálcica, de bordes facetados, con piel suprayacente eritematoazulada. En ocasiones, la piel puede atrofiarse, dar la apariencia de una ampolla e, incluso, extruir material cálcico. El diagnóstico se sospecha por la presentación clínica característica y los estudios de imágenes complementarios. El diagnóstico definitivo es por los hallazgos histológicos. La extirpación quirúrgica es el tratamiento de elección. Se presentan los datos epidemiológicos, clínicos, estudios complementarios y técnicas quirúrgicas empleadas de 149 pilomatrixomas resecados en 137 pacientes tratados en los Servicios de Dermatología de los hospitales de pediatría Dr. Pedro de Elizalde y Prof. Dr. Juan P. Garrahan.

Understanding the mechanical loading environment and resulting joint mechanics for activities of daily living in total knee arthroplasty is essential to continuous improvement in implant design. Although survivorship of these devices is good, a substantial number of patients report dissatisfaction with the outcome of their procedure. Knowledge of in vivo kinematics and joint loading will enable improvement in preclinical assessment and refinement of implant geometry. The purpose of this investigation was to describe the mechanics of total knee arthroplasty during a variety of activities of daily living (gait, walking down stairs, and chair rise/sit). Estimates of muscle forces, tibial contact load, location, and pressure distribution was performed through a combination of mobile fluoroscopy data collection, musculoskeletal modeling, and finite element simulation. For the activities evaluated, joint compressive load was greatest during walking down stairs; however, the highest contact pressure occurred during chair rise/sit. The joint contact moment in the frontal plane was mainly varus for gait and walking down stairs, while it was valgus during chair rise/sit. Excursion of the center of pressure on the tibial component was similar during each activity and between the medial and lateral sides. The main determinants of center of pressure location were internal-external rotation, joint load, and tibial insert conformity. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1576-1587, 2016.

Resume Objectifs Le basketball feminin est un sport de plus en plus competitif, engendrant une augmentation des contacts. Le but de cette etude etait de determiner l’incidence et les caracteristiques des blessures au sein d’une equipe francaise de basketball de haut niveau, afin de definir des strategies preventives. Materiels et methodes Dans cette etude prospective sur neuf mois, les blessures ont ete definies et recueillies selon la methode developpee par le Comite international olympique. Resultats L’incidence totale des blessures etait de 11,3/1000 h de pratique, avec 8,3/1000 h de pratique durant l’entrainement et 144,0/1000 h de pratique en competition (48,3/1000 athletes-exposes). Les membres inferieurs etaient les plus touches (58,9 %) avec les lesions musculaires de cuisse (13,7 %) et les entorses de cheville (11,8 %). Les traumatismes par contact etaient les plus frequents (33,3 %). Cinquante et un pour cent des blessures engendraient un arret sportif, 73,1 % de ces blessures etaient mineures ( Conclusion Cette etude, utilisant une methodologie prospective et rigoureuse, nous permet d’envisager des orientations de strategies de prevention des blessures, centrees sur les blessures qui se sont averees etre les plus frequentes et/ou les plus graves. Ces strategies de prevention pourront etre des bilans isocinetiques des flechisseurs et extenseurs du genou, le renforcement musculaire des membres inferieurs et la proprioception de cheville.

Lipoblastoma is part of tumors derived from adipose tissue. It is a benign neoplasm that can be localized or diffuse, affecting children in early childhood and usually located in the trunk and extremities. These tumors are uncommon in the pediatric age, but when one of them is present, it is a challenge that we must resolve quickly due to the risk of malignancy that involves other similar neoplastic lesions. The preoperative diagnosis is difficult, because the imaging methods do not provide specific information that allows us to differentiate them from other tumors, such as liposarcomas. The definitive diagnosis is anatomopathological and, in doubtful cases, cytogenetic confirmation is necessary. We present the case of a 14-month-old boy with diagnosis of large sized lipoblastoma of retroperitoneal localization.

As fixation of cementless total knee replacement components during the first 4–6 weeks after surgery is crucial to establish bony ingrowth into the porous surface, several studies have quantified implant-bone micromotion. Relative motion between the tray and bone can be measured in vitro, but the full micromotion contour map cannot typically be accessed experimentally. Finite element models have been employed to estimate the full micromotion map, but have not been directly validated over a range of loading conditions. The goal of this study was to develop and validate computational models for the prediction of tray-bone micromotion under simulated activities of daily living. Gait, stair descent and deep knee bend were experimentally evaluated on four samples of a cementless tibial tray implanted into proximal tibial Sawbones™ constructs. Measurements of the relative motion between the tray and the anterior cortical shell were collected with digital image correlation and used to validate a finite element model that replicated the experiment. Additionally, a probabilistic analysis was performed to account for experimental uncertainty and determine model sensitivity to alignment and frictional parameters. The finite element models were able to distinguish between activities and capture the experimental trends. Best-matching simulations from the probabilistic analysis matched measured displacement with an average root mean square (RMS) difference of 14.3 µm and Pearson-product correlation of 0.93, while the mean model presented an average RMS difference of 27.1 µm and a correlation of 0.8. Maximum deviations from average experimental measurements were 40.5 and 87.1 µm for the best-matching and average simulations, respectively. The computational pipeline developed in this study can facilitate and enhance pre-clinical assessment of novel implant components.

Lipoblastoma is part of tumors derived from adipose tissue. It is a benign neoplasm that can be localized or diffuse, affecting children in early childhood and usually located in the trunk and extremities. These tumors are uncommon in the pediatric age, but when one of them is present, it is a challenge that we must resolve quickly due to the risk of malignancy that involves other similar neoplastic lesions. The preoperative diagnosis is difficult, because the imaging methods do not provide specific information that allows us to differentiate them from other tumors, such as liposarcomas. The definitive diagnosis is anatomopathological and, in doubtful cases, cytogenetic confirmation is necessary. We present the case of a 14-month-old boy with diagnosis of large sized lipoblastoma of retroperitoneal localization.El lipoblastoma forma parte de los tumores derivados del tejido adiposo. Es una neoplasia benigna que se puede presentar de forma localizada o difusa, que afecta a niños en la primera infancia y que, generalmente, se localiza en el tronco y las extremidades. Estos tumores son poco frecuentes en la edad pediátrica, pero cuando uno de ellos se presenta, constituye un desafío que se debe resolver rápidamente por el riesgo de malignidad que implican otras lesiones neoplásicas, de similares características. El diagnóstico preoperatorio es dificultoso, ya que los métodos por imágenes no aportan información específica que permita diferenciarlos de otros tumores, como los liposarcomas. El diagnóstico definitivo es anatomopalógico y, en casos dudosos, es necesaria la confirmación citogenética. Se presenta el caso de un niño de 14 meses de edad con diagnóstico de lipoblastoma de localización retroperitoneal de gran tamaño.

Chemical radiolytic oxidation induced by OH addition on 1-(2-furan-2-yl-5-hydroxy6-hydroxymethyl-[1,3]dioxan-4-yl)-ethan-1,2-diol (sorbitylfurfural, SF) leads, in the presence of controlled amounts of oxygen, to a permanent functional modification of the target molecule. The yield of conversion reaches 60% of the starting material. LC-MS analysis allowed the identification, as final products, of carboxylic acids, butenal and hydroxy-furan derivatives in which the sugar chain remains unbroken, while the furanic ring is attacked first by OH and then by oxygen, giving in succession an intra-/inter-molecular rearrangement of the allylperoxyl radicals thus formed. The proposed oxidation of the furanic ring envisages the peroxyl intermediates undergoing mono- and/or bi-molecular reactions; a reaction path has been outlined and is reported here. The presence of unsaturated bonds in the final products could provide a further site for radical scavenger activity. Therefore, the fast reaction with O-2 and the rearrangement of the produced peroxyl radicals to species, which are likely to be effective OH-capturers, reinforces the antioxidant ability of SF.

The reaction of dihydroartemisinin (DHA) with solvated electrons (e(solv)(-)) generated under radiolytic conditions showed high pH dependence. The reduction performed under neutral conditions led to the formation of compound P1 deriving from the initial alkoxyl radical as the only detectable product. (C) 2013 Elsevier Ltd. All rights reserved.

In the last 30 years oligonucleotides i.e., relatively short polymers (usually 12-24 units long) based on DNA structure, have found a widespread use in biochemical studies and as biochemical probes and chemotherapeutic agents for the downregulation of genetic expression or for exon skipping. Here we present a short review of studies from our laboratories on the synthesis and applications of different kind of conjugates to address some of these techniques. Preparation of conjugates with small alkyl groups, intercalators, fluorescent oligothiophenes, and lipophilic bile-acids will be discussed.

Pemphigus vulgaris is a chronic disease that is characterized by flaccid blisters and erosions, caused by immunoglobulin G autoantibodies against epidermal components. It is highly unusual in the pediatric population; it represents the 1.4 - 2.9% of the total cases. We present a case of pemphigus vulgaris in a 12 year old girl, which has implied a challenge both in its diagnosis and in its treatment.

Pemphigus vulgaris is a chronic disease that is characterized by flaccid blisters and erosions, caused by immunoglobulin G autoantibodies against epidermal components. It is highly unusual in the pediatric population; it represents the 1.4 - 2.9% of the total cases. We present a case of pemphigus vulgaris in a 12 year old girl, which has implied a challenge both in its diagnosis and in its treatment.El pénfigo vulgar es una enfermedad crónica que se caracteriza por ampollas fláccidas y erosiones, causadas por un fenómeno autoinmune con autoanticuerpos inmunoglobulina G circulantes contra componentes de la epidermis. Su presentación en la infancia es altamente infrecuente; representa el 1,4%-2,9% de todos los casos de pénfigo vulgar. Presentamos un caso de pénfigo vulgar en una niña de 12 años, que implicó un desafío en su diagnóstico y terapéutica.

Quantification of muscle moment arms is important for clinical evaluation of muscle pathology and treatment, and for estimating muscle and joint forces in musculoskeletal models. Moment arms estimated with musculoskeletal models often assume a default motion of the knee derived from measurements of passive cadaveric flexion. However, knee kinematics are unique to each person and activity. The objective of this study was to estimate moment arms of the knee muscles with in vivo subject- and activity-specific kinematics from seven healthy subjects performing seated knee extension and single-leg lunge to show changes between subjects and activities. 3D knee motion was measured with a high-speed stereo-radiography system. Moment arms of ten muscles were estimated in OpenSim by replacing the default knee motion with in vivo measurements. Estimated inter-subject moment arm variability was similar to previously reported in vitro measurements. RMS deviations up to 9.0 mm (35.2% of peak value) were observed between moment arms estimated with subject-specific knee extension and passive cadaveric motion. The degrees of freedom that most impacted inter-activity differences were superior/inferior and anterior/posterior translations. Musculoskeletal simulations used to estimate in vivo muscle forces and joint loads may provide significantly different results when subject- and activity-specific kinematics are implemented.

Multielectron systems as possible components of molecular electronics devices are attracting compelling experimental and theoretical interest. Here we studied by electrochemical scanning tunneling techniques (EC-STMicroscopy and EC-STSpectroscopy) the electron transport properties of a redox molecule endowed with two redox levels, namely, the hydroquinone/quinone (H(2)Q/Q) couple. By forming self-assembled monolayers on Au(111) of oligo-phenylene-vinylene (OPV) derivatized H(2)Q/Q moieties, we were able to explore the features of the tunneling current/overpotential relation in the EC-STS setup. The behavior of the tunneling current sheds light onto the mechanism of electron transport involving the redox levels of the H(2)Q/Q redox pair coupled to tip and substrate electrodes

Versatile synthetic methods towards a variety of thiophene-nucleobase hybrid systems are reported. Adenine- and thymine-based modified nucleosides characterized by a bithiophene unit linked to the C5' or C8 position through an ethylenamino or an ethylensulfanyl bridge were synthesized and successfully polymerized in the presence of FeCl(3) . The self-organization properties of the pure polymers as well as their mixtures - with complementary nucleobases - were investigated by means of optical microscopy and AFM in cast film showing complex supramolecular structures resulting from the interplay of multiple intermolecular interactions.

Musculoskeletal models are powerful tools that allow biomechanical investigations and predictions of muscle forces not accessible with experiments. A core challenge modelers must confront is validation. Measurements of muscle activity and joint loading are used for qualitative and indirect validation of muscle force predictions. Subject-specific models have reached high levels of complexity and can predict contact loads with surprising accuracy. However, every deterministic musculoskeletal model contains an intrinsic uncertainty due to the high number of parameters not identifiable in vivo. The objective of this work is to test the impact of intrinsic uncertainty in a scaled-generic model on estimates of muscle and joint loads. Uncertainties in marker placement, limb coronal alignment, body segment parameters, Hill-type muscle parameters, and muscle geometry were modeled with a global probabilistic approach (multiple uncertainties included in a single analysis). 5–95% confidence bounds and input/output sensitivities of predicted knee compressive loads and varus/valgus contact moments were estimated for a gait activity of three subjects with telemetric knee implants from the “Grand Challenge Competition.” Compressive load predicted for the three subjects showed confidence bounds of 333 ± 248 N, 408 ± 333 N, and 379 ± 244 N when all the sources of uncertainty were included. The measured loads lay inside the predicted 5–95% confidence bounds for 77%, 83%, and 76% of the stance phase. Muscle maximum isometric force, muscle geometry, and marker placement uncertainty most impacted the joint load results. This study demonstrated that identification of these parameters is crucial when subject-specific models are developed.

Congenital intestinal lymphangiectasis (LIP) is a protein-losing enteropathy that appears sporadically in children. It begins with edema due to hypoproteinemia and hypoalbuminemia, and in some cases with ascites, immunodeficience and hypocalcemic tetania. The purpose of this report is to present two patients with LIP which appeared during the first year of life. The diagnosis was certificated by upper gastrointestinal videoendoscopy and histological findings. Both patients were treated with a new formula containing mean chain triglycerides with an adequate response, not obtained before with a common semielemental formula.

The aim of the present study was to investigate the effects of the alpha2-adrenoceptor antagonist yohimbine on blood pressure and heart rate (HR) regulation, as well as on adrenergic and serotoninergic neurotransmission, in fructose hypertensive (F) rats. The anterior hypothalamic area of control (C) and F rats was perfused with Ringer's solution containing 10 and 100 microg/mL yohimbine through a microdialysis concentric probe. The effects of yohimbine on mean arterial pressure (MAP) and HR, as well as on hypothalamic dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) levels, were measured according to perfusion time. Although intrahypothalamic perfusion of yohimbine increased blood pressure in C rats (DeltaMAP 9 +/- 1 and 11 +/- 2 mmHg for 10 and 100 microg/mL yohimbine, respectively; P < 0.05 vs Ringer's perfusion), the alpha-adrenoceptor antagonist did not modify MAP in F. Intrahypothalamic yohimbine had no effect on HR at either concentration tested. Intrahypothalamic perfusion of 10 and 100 microg/mL yohimbine increased DOPAC levels in C rats (135 +/- 6 and 130 +/- 5% of basal levels, respectively; both n = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 +/- 6 and 102 +/- 6% of basal levels, respectively; both n = 6). In both C and F rats, yohimbine administration induced an increase in 5-HIAA dialysate levels. The results of the present study support the notion that alpha2-adrenoceptor tone of the anterior hypothalamus of normotensive rats, which contributes to normal blood pressure regulation, is not involved in the control of HR in either normotensive C or hypertensive F rats. The absence of changes in MAP after yohimbine perfusion in F rats suggests that the alpha2-adrenoceptor tone could be decreased in this group of rats and that this may be responsible for the maintenance of hypertension in this model. Intrahypothalamic perfusion of yohimbine increased DOPAC in the dialysate only in C rats, suggesting changes in presynaptic alpha2-adrenoceptor activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not differ between C and F groups.