Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct Activation of NADPH Oxidase 2 by 2-Deoxyribose-1-Phosphate Triggers Nuclear Factor Kappa B-Dependent Angiogenesis

Abstract Aims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells. Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice. Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex. Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130.
Students’ Perceptions of Workshop Based Introductory Macroeconomics Tutorials: A Survey

The declining popularity of Economics courses, evident in the last decade, has fueled a debate on the nature of Economics units and the way in which they are taught in tertiary institutions. The effectiveness of traditional teaching methods has been questioned as lecturers search for alternative ways of presenting material and engaging students. In recent times, workshop-based/cooperative tutorials have become more popular in promoting deeper learning. This paper assesses the application of such an approach at a large tertiary institution. It evaluates student perceptions of this tutorial method in an Introductory Macroeconomics first-year unit. An anonymous questionnaire was used. Whilst the sample size is small (n = 56), the results are important in that this is the first such study in Macroeconomics. Students found workshop-based tutorials useful, preferred them over lecture style tutorials, and found that they fostered inclusivity. The importance of tutorials per se, is reiterated. Students state that tutorials are an important adjunct to lectures. This study also looks at students’ study habits: finding that on average they spend less than one hour per week studying Economics and most prepare only occasionally for tutorials. The sample studied indicates that there are notable differences in the perceptions of tutorials and teaching methods between the genders and between local and international students. This may impact on the way in which tutorials are conducted effectively.
Risk Indicators and Interceptive Treatment Alternatives for Palatally Displaced Canines

The present article reviews diagnostic, prognostic, and therapeutic aspects related to palatal displaced canines (PDCs) and their possible evolution to palatally impacted canines (PICs). Through the analysis of the relevant literature, a series of dental anomalies can be identified that present with a significant clinical association with PDC. Because these tooth disturbances may appear before PDC, they represent risk indicators for the occurrence of the eruption anomaly of the maxillary permanent canine. The second part of this work describes comparatively the effectiveness of several interceptive treatment approaches to PDC to avoid the evolution from PDC to PIC. In particular, the extraction of the deciduous canine, alone or in combination with orthodontic forces aimed to prevent the physiological mesial movement of the upper permanent molar, appears to be able to increase by 2 to 3 times the rate of eruption of PDCs (diagnosed on a panoramic radiograph) with respect to that which occurs in untreated subjects with PDC (spontaneous eruption in about one third of the cases). Rapid maxillary expansion in the early developmental stages may represent a valid alternative for the interceptive treatment of PDCs (diagnosed on a posteroanterior cephalogram). Although genetic factors are known to play a fundamental role in the etiology of PDC (and subsequent PIC), it appears that environmental local factors can be affected by orthodontic/orthopedic approaches during the pathogenetic evolution process leading from PDC to final PIC.
Coherent patterns in long‐term sea‐level variability trends derived from long‐term tide gauge measurements

Global long‐term sea‐level variability trends and regional coherence patterns were mapped based on hourly sea‐level time series data from the 29 longest operating tide gauge stations distributed worldwide. We split sea‐level variability into three frequency bands: (1) small‐scale synoptic bands (1–3 d), (2) large‐scale synoptic bands (3–10 d) and (3) planetary‐scale bands (10–100 d). We then calculated seasonal and annual trends. The most coherent result obtained involved a significant decrease in sea‐level variability over the tropical and subtropical Pacific, particularly at the synoptic scale frequencies. Several other coherent regions were found and linked to changes in the global atmosphere. Copyright © 2012 Royal Meteorological Society
Polyethylene wear vector in vivo: A three‐dimensional analysis using retrieved acetabular components and radiographs

Polyethylene wear of the acetabular component can be described as one or more vectors. To help clarify the mechanisms of wear advancement in vivo, we used a combination of retrieved implants and radiographs to describe the three‐dimensional wear vectors in total hip arthroplasty. The wear vectors in 41 retrieved implants from a single manufacturer were measured with use of the shadowgraph technique, and the spatial orientation of each implant was calculated from serial anteroposterior pelvic radiographs. On the basis of the combination of the wear vector in the implant and implant orientation in the pelvis, the wear vectors in vivo were determined. The mean wear vector was directed 8.1° lateral in the coronal plane and 4.1° posterior in the sagittal plane. The wear vector in vivo showed a relatively wide range of directions, not necessarily coinciding with the commonly presumed resultant force in the hip. The wear vectors were not associated with the spatial orientation of the acetabular components, but cups with impingement demonstrated more anterior wear than did those without impingement. Our results suggest that the process of polyethylene wear is not as simple as previously described and that several factors influence advancement of wear in vivo.
Automatic processing of emotional words during an emotional Stroop task

There is evidence that early event-related potential components, such as the early posterior negativity (EPN; 200–300 ms), are modulated by emotional words. This study addressed the automaticity of this early response in an emotional Stroop task. The results show that the EPN was modulated by emotional connotation. In addition, an enhanced frontal P3 and an enhanced, more broadly distributed, late positive potential emerged as response to emotional words. The present results suggest that this early event-related potential activity represents the fast and automatic processing of emotional words. Furthermore, as the EPN originates from the posterior visual association cortex, the present results suggest a role of these areas in the automatic processing of emotional connotation.
Antidiabetic and Anti-oxidant Activity of Aegle marmelos Extract in Streptozotocin-Induced Diabetic Rats

The aqueous extract of Aegle marmelos Correa. fruits (AMFEt) was studied in normal and streptozotocin (STZ) diabetic rats and anti-lipid peroxidative activity was studied in hepatic and renal tissues in diabetic rats. Oral administration of AMFEt for 30 days (twice a day) prevented significantly the STZ-induced hyperglycaemia and hypoinsulinemia. The extract also produced a significant decrease in peroxidation products, viz., thiobarbituric acid reactive substances and hydroperoxides in diabetic rats. The activity of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase was found to be increased in the hepatic and renal tissues of diabetic animals treated with AMFEt. AMFEt, at a dose of 250 mg/kg, was more effective than glibenclamide and reversed all the values to near normal status. Thus, AMFEt exhibits antidiabetic and anti-oxidative activity in STZ-diabetic rats.
Bacteriemia por Listeria monocytogenes: análisis de 110 casos

Fundamento y objetivo: En los ultimos anos se ha observado un aumento del numero de casos de listeriosis atendidos en nuestro centro. El objetivo del presente estudio ha sido analizar la comorbilidad, la forma de presentacion clinica y el pronostico de los episodios de bacteriemia por Listeria monocytogenes diagnosticados a lo largo de 15 anos. Pacientes y metodo: Entre enero de 1991 y abril de 2005 se recogio de forma prospectiva la historia clinica de 110 pacientes con bacteriemia por L. monocytogenes. En todos los casos se obtuvo informacion demografica, sobre la forma de presentacion clinica, tratamiento antimicrobiano y evolucion de la infeccion. Resultados: Entre 1991 y 1995 se presentaron 20 casos (18,2%); entre 1996 y 2000 hubo 27 (24,6%) y entre 2001 y abril de 2005 se registraron 63 (57,3%) (p < 0,05). Cien pacientes (90,9%) tenian una o mas enfermedades asociadas a inmunodepresion y 54 (49,9%) recibian corticoides. En 63 casos la infeccion se presento en forma de bacteriemia primaria, en 35 se localizo en el sistema nervioso central y en 6, en el liquido ascitico (pacientes con cirrosis hepatica). Trece pacientes (11,8%) presentaron shock septico y 18 (16,3%) fallecieron. La mortalidad de los pacientes con meningitis tratados empiricamente con una cefalosporina de tercera generacion fue del 50% (5/10), frente al 12% (3/25) en los que inicialmente recibieron un antibiotico potencialmente activo frente a L. monocytogenes (p = 0,05). Conclusiones: La frecuencia de infeccion por L. monocytogenes ha aumentado en los ultimos anos. Los pacientes inmunodeprimidos deberian conocer las recomendaciones encaminadas a evitar la ingesta de alimentos potencialmente contaminados. En la eleccion del tratamiento antibiotico empirico en caso de fiebre o meningitis en el paciente inmunodeprimido se debe tener en cuenta la falta de actividad de las cefalosporinas contra L. monocytogenes.
Chemotransport contributes to the effect of oscillatory fluid flow on human bone marrow stromal cell proliferation

Mechanical loads produce a diverse set of biophysical signals that may regulate bone cell activity, but accumulating evidence suggests that interstitial fluid flow is the primary signal that bone cells perceive. Because we previously demonstrated that oscillatory fluid flow increases human bone marrow stromal cell proliferation, we investigated the contribution of fluid shear stress and chemotransport, two stimuli induced by interstitial fluid flow. Alterations in flow rate at a constant peak shear stress were associated with decreases in oscillatory fluid flow‐induced marrow stromal cell proliferation, while variations in peak fluid shear stress had no significant effect. Modulation of marrow stromal cell proliferation by flow rate may be attributed to changes in the release of ATP and intracellular calcium signaling. We found that if the flow rate is decreased while maintaining a constant peak fluid shear stress, marrow stromal cells release less ATP into the extracellular environment. Moreover, as the flow rate decreased fewer cells respond to fluid flow with an increase in intracellular calcium concentration. These data suggest that chemotransport is a prerequisite for marrow stromal cells to respond to interstitial fluid flow. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:918–924, 2008
Targeted and Off-Target (Bystander and Abscopal) Effects of Radiation Therapy: Redox Mechanisms and Risk/Benefit Analysis

Abstract Significance: Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called target theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death. In cancer therapy, the Poisson law and linear quadratic mathematical models have been used to describe the probability of hits per cell as a function of the radiation dose. Recent Advances: However, in the last 20 years, many studies have shown that radiation generates “danger” signals that propagate from irradiated to nonirradiated cells, leading to bystander and other off-target effects. Critical Issues: Like for targeted effects, redox mechanisms play a key role also in off-target effects through transmission of ROS and reactive nitrogen species (RNS), and also of cytokines, ATP, and extracellular DNA. Particularly, nuclear factor kappa B is essential for triggering self-sustained production of ROS and RNS, thus making the bystander response similar to inflammation. In some therapeutic cases, this phenomenon is associated with recruitment of immune cells that are involved in distant irradiation effects (called “away-from-target” i.e., abscopal effects). Future Directions: Determining the contribution of targeted and off-target effects in the clinic is still challenging. This has important consequences not only in radiotherapy but also possibly in diagnostic procedures and in radiation protection.
Role of Nutrition in Environmental Lung Disease

Lung diseases represent a major burden in morbidity and mortality. Diet has generated growing interest because of its potential impact in the genesis and evolution of these diseases by modulating the effect of environmental exposure. This article examines the relationships between dietary factors, including minerals, antioxidant vitamins, and omega -3 and -6 fatty acids, and environmental lung diseases. The potential mechanisms by which dietary factors may affect respiratory health are reviewed, and epidemiological evidence for the link between diet and asthma, chronic obstructive airways disease, and lung cancer is discussed. At present, most of the available evidence for nonmalignant lung diseases comes from cross-sectional studies and suggests a beneficial impact of antioxi dant vitamins, in particular vitamin C and to a lesser extent vitamin E, on lung diseases. Prospective and retrospective studies have reported a lower risk of lung cancer among populations with high levels of fruit or vegetable, or both, consumption. There is a need for further research in experimental and epidemiological settings to better understand the pathophysiological effects of antioxidant vitamins, omega-3 fatty acids, and other nutri ents on lung tissues
Early dynamization by reduced fixation stiffness does not improve fracture healing in a rat femoral osteotomy model

Dynamization of fracture fixation is used clinically to improve the bone healing process. However, the effect of early dynamization remains controversial. This study evaluated the effect of early dynamization, by reduced stiffness of fixation on callus stiffness and size after 5 weeks of healing in a rat diaphyseal femoral osteotomy. An external unilateral fixator allowed either a rigid (R‐group; n = 8) or a flexible (F‐group; n = 8) fixation. The dynamized group (D‐group: n = 8) had a rigid fixation for 1 week, and then a flexible fixation for the remaining 4 weeks. The pre‐ and postoperative activity of the rats was measured. After 5 weeks, the rats were sacrificed, and healing was evaluated by biomechanical and densitometric methods. The R‐group had a higher activity more closely approaching preoperative levels, compared to the D‐group throughout all time points measured. This difference was significant after 14 days and 21 days. The flexural rigidity of the R‐group was 82% (tested in the anterior‐posterior direction; p = 0.01) and 93% (tested in the medial‐lateral direction; p = 0.002) greater than the flexural rigidity of the D‐group. The rigid fixation led to a stiffer callus with a smaller callus volume, but better mineralized tissue in the whole callus and at the level of the osteotomy gap than the flexible or the dynamized fixation. Early dynamization did not improve healing compared to rigid or flexible fixation in a rat femoral osteotomy model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:22–27, 2009
Porous tantalum and poly‐ε‐caprolactone biocomposites for osteochondral defect repair: Preliminary studies in rabbits

Currently, various techniques are in use for the repair of osteochondral defects, none of them being truly satisfactory and they are often two step procedures. Comorbidity due to cancellous bone harvest from the iliac crest further complicates the procedure. Our previous in vitro studies suggest that porous tantalum (TM) or poly‐ε‐caprolactone scaffolds (PCL) in combination with periosteal grafts could be used for osteochondral defect repair. In this in vivo study, cylindrical osteochondral defects were created on the medial and lateral condyles of 10 rabbits and filled with TM/periosteum or PCL/periosteum biosynthetic composites (n = 8 each). The regenerated osteochondral tissue was then analyzed histologically, and evaluated in an independent and blinded manner by five different observers using a 30‐point histological score. The overall histological score for PCL/periosteum was significantly better than for TM/periosteum. However, most of the regenerates were well integrated with the surrounding bone (PCL/periosteum, n = 6.4; TM/periosteum, n = 7) along with partial restoration of the tidemark (PCL/periosteum, n = 4.4; TM/periosteum, n = 5.6). A cover of hyaline‐like morphology was found after PCL/periosteum treatment (n = 4.8), yet the cartilage yields were inconsistent. In conclusion, the applied TM and PCL scaffolds promoted excellent subchondral bone regeneration. Neo‐cartilage formation from periosteum supported by a scaffold was inconsistent. This is the first study to show in vivo results of both PCL and TM scaffolds for a novel approach to osteochondral defect repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:141–148, 2010
Lymphocyte proliferation responses in patients with pseudotumors following metal‐on‐metal hip resurfacing arthroplasty

Locally destructive soft tissue pseudotumor has been reported in patients following metal‐on‐metal hip resurfacing arthroplasty (MoMHRA). A delayed hypersensitivity reaction type IV to nickel (Ni), chromium (Cr), or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of metal‐induced systemic hypersensitivity in patients with MoMHRA, both with and without pseudotumor by measuring lymphocyte proliferation responses to metals. A total of 92 patients were investigated: (1) MoMHRA patients with pseudotumors (nine female, one male); (2) MoMHRA patients without pseudotumors (30 female, 30 male); and (3) age‐matched control subjects without metal implants (9 female, 13 male). The venous blood samples were collected for serum Ni, Co, and Cr ion level measurements and lymphocyte transformation tests (LTT). A higher incidence and level of enhanced lymphocyte reactivity only to Ni was found in patients with MoMHRA compared to the patients without MoM implants, reflecting exposure and immune reactivity. However, lymphocyte reactivity to Co, Cr, and Ni did not significantly differ in patients with pseudotumors compared to those patients without pseudotumors. This suggests that systemic hypersensitivity type IV reactions, as measured by lymphocyte proliferation response to these metals, may not be the dominant biological reaction involved in the occurrence of the soft tissue pseudotumors. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:444–450, 2010
Moment arms of the shoulder muscles during axial rotation

The objective of the present study was to determine the instantaneous moment arms of 18 major muscle sub‐regions crossing the glenohumeral joint in axial rotation of the humerus during coronal‐plane abduction and sagittal‐plane flexion. The tendon‐excursion method was used to measure instantaneous muscle moment arms in eight entire upper‐extremity cadaver specimens. The results showed that the inferior subscapularis was the largest internal rotator; its rotation moment arm peaks were 24.4 and 27.0 mm during abduction and flexion, respectively. The inferior infraspinatus and teres minor were the greatest external rotators; their respective rotation moment arms peaked at 28.3 and 26.5 mm during abduction, and 23.3 and 22.1 mm during flexion. The two supraspinatus sub‐regions were external rotators during abduction and internal rotators during flexion. The latissimus dorsi and pectoralis major behaved as internal rotators throughout both abduction and flexion, with the three pectoralis major sub‐regions and middle and inferior latissimus dorsi displaying significantly larger internal rotation moment arms with the humerus adducted or flexed than when abducted or extended (p < 0.001). The deltoid behaved either as an internal rotator or an external rotator, depending on the degree of humeral abduction and axial rotation. Knowledge of moment arm differences between muscle sub‐regions may assist in identifying the functional effects of muscle sub‐region tears, assist surgeons in planning tendon transfer surgery, and aid in the development and validation of biomechanical computer models. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:658–667, 2011