[Artículo traducido] Manejo de metástasis sintomáticas de columna: un enfoque multidisciplinario basado en un diagrama de flujo / Management of symptomatic spine metastases: A multidisciplinary approach based flow-chart

Describimos un algoritmo para el manejo de las metástasis espinales en el que la importancia de los parámetros individuales varía dependiendo del momento en el que se contemplan.Cada paciente sigue su propio proceso secuencial «personal» que no necesariamente considera todos los parámetros cada vez, ya que algunos pueden ser irrelevantes a la hora de elegir el tipo de tratamiento para ese individuo. Por ejemplo, un paciente en mal estado general con una puntuación ASA alta generalmente no es candidato para la cirugía, independientemente de la naturaleza del tumor primario o del número de metástasis. Para este paciente, el elemento más importante sería la sensibilidad del tumor al tratamiento adyuvante. Del mismo modo, un paciente con lesión aguda y progresiva de la médula espinal se sometería a descompresión quirúrgica y estabilización sin considerar una intervención más agresiva.(AU)

We described an algorithm for the management of spinal metastases in which the importance of single parameters varies depending on when they are contemplated.Each patient follows his own «personal» sequential process which does not necessarily consider all the parameters each time as some may be irrelevant for the purpose of choosing the type of treatment for that single individual. For instance, a patient in general poor condition with a high ASA score is usually not a candidate for surgery, regardless of the primary tumor nature or the number of metastases. For this patient, the most important element would be the sensitivity of the tumor to adjuvant treatment. Similarly, a patient with acute and progressive spinal cord injury would undergo surgical decompression and stabilization without considering a more strenuous intervention.(AU)

Management of symptomatic spine metastases: A multidisciplinary approach based flow-chart / Manejo de metástasis sintomáticas de columna: un enfoque multidisciplinario basado en un diagrama de flujo

Describimos un algoritmo para el manejo de las metástasis espinales en el que la importancia de los parámetros individuales varía dependiendo del momento en el que se contemplan.Cada paciente sigue su propio proceso secuencial «personal» que no necesariamente considera todos los parámetros cada vez, ya que algunos pueden ser irrelevantes a la hora de elegir el tipo de tratamiento para ese individuo. Por ejemplo, un paciente en mal estado general con una puntuación ASA alta generalmente no es candidato para la cirugía, independientemente de la naturaleza del tumor primario o del número de metástasis. Para este paciente, el elemento más importante sería la sensibilidad del tumor al tratamiento adyuvante. Del mismo modo, un paciente con lesión aguda y progresiva de la médula espinal se sometería a descompresión quirúrgica y estabilización sin considerar una intervención más agresiva.(AU)

We described an algorithm for the management of spinal metastases in which the importance of single parameters varies depending on when they are contemplated.Each patient follows his own «personal» sequential process which does not necessarily consider all the parameters each time as some may be irrelevant for the purpose of choosing the type of treatment for that single individual. For instance, a patient in general poor condition with a high ASA score is usually not a candidate for surgery, regardless of the primary tumor nature or the number of metastases. For this patient, the most important element would be the sensitivity of the tumor to adjuvant treatment. Similarly, a patient with acute and progressive spinal cord injury would undergo surgical decompression and stabilization without considering a more strenuous intervention.(AU)

Management of symptomatic spine metastases: A multidisciplinary approach based flow-chart. / [Artículo traducido] Manejo de metástasis sintomáticas de columna: un enfoque multidisciplinario basado en un diagrama de flujo.

We described an algorithm for the management of spinal metastases in which the importance of single parameters varies depending on when they are contemplated. Each patient follows his own «personal¼ sequential process which does not necessarily consider all the parameters each time as some may be irrelevant for the purpose of choosing the type of treatment for that single individual. For instance, a patient in general poor condition with a high ASA score is usually not a candidate for surgery, regardless of the primary tumor nature or the number of metastases. For this patient, the most important element would be the sensitivity of the tumor to adjuvant treatment. Similarly, a patient with acute and progressive spinal cord injury would undergo surgical decompression and stabilization without considering a more strenuous intervention.

Management of symptomatic spine metastases: A multidisciplinary approach based flow-chart.

We described an algorithm for the management of spinal metastases in which the importance of single parameters varies depending on when they are contemplated. Each patient follows his own "personal" sequential process which does not necessarily consider all the parameters each time as some may be irrelevant for the purpose of choosing the type of treatment for that single individual. For instance, a patient in general poor condition with a high "ASA" score is usually not a candidate for surgery, regardless of the primary tumor nature or the number of metastases. For this patient, the most important element would be the sensitivity of the tumor to adjuvant treatment. Similarly, a patient with acute and progressive spinal cord injury would undergo surgical decompression and stabilization without considering a more strenuous intervention.

Multi-angle in situ dynamic light scattering at a neutron spin echo spectrometer.

A new sample environment, called Bio-Oven, has been built for the Neutron Spin Echo (NSE) Spectrometer J-NSE Phoenix. It provides active temperature control and the possibility to perform Dynamic Light Scattering (DLS) measurements during the neutron measurement. DLS provides diffusion coefficients of the dissolved nanoparticles, and thus one can monitor the aggregation state of the sample on a time scale of minutes during the spin echo measurement times on the order of days. This approach helps to validate the NSE data or to replace the sample when its aggregation state influences the spin echo measurement results. The new Bio-Oven is an in situ DLS setup based on optical fibers decoupling the free space optics around the sample cuvette in a lightproof casing from the laser sources and the detectors. It collects light from three scattering angles simultaneously. Six different values of momentum transfer can be accessed by switching between two different laser colors. Test experiments were performed with silica nanoparticles with diameters ranging from 20 nm up to 300 nm. Their hydrodynamic radii were determined from DLS measurements and compared with the ones obtained by a commercial particle sizer. It was demonstrated that also the static light scattering signal can be processed and gives meaningful results. The protein sample apomyoglobin was used for a long-term test and in a first neutron measurement using the new Bio-Oven. The results prove that the aggregation state of the sample can be followed using in situ DLS along with the neutron measurement.

Self-Similar Dynamics of Large Polymer Rings: A Neutron Spin Echo Study.

This work clarifies the self-similar dynamics of large polymer rings using pulsed-field gradient nuclear magnetic resonance and neutron spin echo spectroscopy. We find center of mass diffusion taking place in three dynamic regimes starting (i) with a strongly subdiffusive domain ⟨r^{2}(t)⟩_{com}∼t^{α} (0.4≤α≤0.65); (ii) a second subdiffusive region ⟨r^{2}(t)⟩_{com}∼t^{0.75} that (iii) finally crosses over to Fickian diffusion. While the t^{0.75} range previously has been found in simulations and was predicted by theory, we attribute the first to the effect of cooperative dynamics resulting from the correlation hole potential. The internal dynamics at scales below the elementary loop size is well described by ring Rouse motion. At larger scales the dynamics is self-similar and follows very well the predictions of the scaling models with preference for the self-consistent fractal loopy globule model.

Fluctuation suppression in microgels by polymer electrolytes.

Structural details of thermoresponsive, cationically poly(N-iso-propylacrylamide-co-methacrylamido propyl trimethyl ammonium chloride) microgels and the influence of the anionic electrolyte polystyrene sulfonate (PSS) on the internal structure and dynamics of the cationic microgels have been studied with a combination of small angle neutron scattering (SANS) and neutron spin echo (NSE) spectroscopy. While SANS can yield information on the overall size of the particles and on the typical correlation length inside the particles, studying the segmental polymer dynamics with NSE gives access to more internal details, which only appear due to their effect on the polymer motion. The segmental dynamics of the microgels studied in this paper is to a large extent suppressed by the PSS additive. Possible scenarios of the influence of the polyanions on the microgel structure and dynamics are discussed.

Efficient data extraction from neutron time-of-flight spin-echo raw data.

Neutron spin-echo spectrometers with a position-sensitive detector and operating with extended time-of-flight-tagged wavelength frames are able to collect a comprehensive set of data covering a large range of wavevector and Fourier time space with only a few instrumental settings in a quasi-continuous way. Extracting all the information contained in the raw data and mapping them to a suitable physical space in the most efficient way is a challenge. This article reports algorithms employed in dedicated software, DrSpine (data reduction for spin echo), that achieves this goal and yields reliable representations of the intermediate scattering function S(Q, t) independent of the selected 'binning'.

J-NSE-Phoenix, a neutron spin-echo spectrometer with optimized superconducting precession coils at the MLZ in Garching.

A novel set of superconducting main precession coils has been built and installed in the Jülich-neutron spin-echo (J-NSE) spectrometer at the Heinz Maier-Leibnitz Zentrum (MLZ) in Garching. These unique new coils comprise a field-integral optimizing field shape, fringe field compensation, and high stability. They yield an enhancement of a factor of 2.5 in the intrinsic field-integral homogeneity, i.e., the resolution. The coil concept has been developed for the ESSENSE instrument proposal for the European Spallation Source. We report on the construction of and on the first results from the new superconducting neutron spin-echo spectrometer at the MLZ in Garching where the coils are the main part of a refurbishment of the J-NSE spectrometer after twenty years of operation.

Polymer dynamics under cylindrical confinement featuring a locally repulsive surface: A quasielastic neutron scattering study.

We investigated the effect of intermediate cylindrical confinement with locally repulsive walls on the segmental and entanglement dynamics of a polymer melt by quasielastic neutron scattering. As a reference, the corresponding polymer melt was measured under identical conditions. The locally repulsive confinement was realized by hydrophilic anodic alumina nanopores with a diameter of 20 nm. The end-to-end distance of the hydrophobic infiltrated polyethylene-alt-propylene was close to this diameter. In the case of hard wall repulsion with negligible local attraction, several simulations predicted an acceleration of segmental dynamics close to the wall. Other than in attractive or neutral systems, where the segmental dynamics is slowed down, we found that the segmental dynamics in the nanopores is identical to the local mobility in the bulk. Even under very careful scrutiny, we could not find any acceleration of the surface-near segmental motion. On the larger time scale, the neutron spin-echo experiment showed that the Rouse relaxation was not altered by confinement effects. Also the entanglement dynamics was not affected. Thus at moderate confinement conditions, facilitated by locally repulsive walls, the dynamics remains as in the bulk melt, a result that is not so clear from simulations.

Regional Risk Assessment for climate change impacts on coastal aquifers.

Coastal aquifers have been identified as particularly vulnerable to impacts on water quantity and quality due to the high density of socio-economic activities and human assets in coastal regions and to the projected rising sea levels, contributing to the process of saltwater intrusion. This paper proposes a Regional Risk Assessment (RRA) methodology integrated with a chain of numerical models to evaluate potential climate change-related impacts on coastal aquifers and linked natural and human systems (i.e., wells, river, agricultural areas, lakes, forests and semi-natural environments). The RRA methodology employs Multi Criteria Decision Analysis methods and Geographic Information Systems functionalities to integrate heterogeneous spatial data on hazard, susceptibility and risk for saltwater intrusion and groundwater level variation. The proposed approach was applied on the Esino River basin (Italy) using future climate hazard scenarios based on a chain of climate, hydrological, hydraulic and groundwater system models running at different spatial scales. Models were forced with the IPCC SRES A1B emission scenario for the period 2071-2100 over four seasons (i.e., winter, spring, summer and autumn). Results indicate that in future seasons, climate change will cause few impacts on the lower Esino River valley. Groundwater level decrease will have limited effects: agricultural areas, forests and semi-natural environments will be at risk only in a region close to the coastline which covers less than 5% of the total surface of the considered receptors; less than 3.5% of the wells will be exposed in the worst scenario. Saltwater intrusion impact in future scenarios will be restricted to a narrow region close to the coastline (only few hundred meters), and thus it is expected to have very limited effects on the Esino coastal aquifer with no consequences on the considered natural and human systems.

Climate change impact assessment on Veneto and Friuli Plain groundwater. Part I: an integrated modeling approach for hazard scenario construction.

Climate change impacts on water resources, particularly groundwater, is a highly debated topic worldwide, triggering international attention and interest from both researchers and policy makers due to its relevant link with European water policy directives (e.g. 2000/60/EC and 2007/118/EC) and related environmental objectives. The understanding of long-term impacts of climate variability and change is therefore a key challenge in order to address effective protection measures and to implement sustainable management of water resources. This paper presents the modeling approach adopted within the Life+ project TRUST (Tool for Regional-scale assessment of groUndwater Storage improvement in adaptation to climaTe change) in order to provide climate change hazard scenarios for the shallow groundwater of high Veneto and Friuli Plain, Northern Italy. Given the aim to evaluate potential impacts on water quantity and quality (e.g. groundwater level variation, decrease of water availability for irrigation, variations of nitrate infiltration processes), the modeling approach integrated an ensemble of climate, hydrologic and hydrogeologic models running from the global to the regional scale. Global and regional climate models and downscaling techniques were used to make climate simulations for the reference period 1961-1990 and the projection period 2010-2100. The simulation of the recent climate was performed using observed radiative forcings, whereas the projections have been done prescribing the radiative forcings according to the IPCC A1B emission scenario. The climate simulations and the downscaling, then, provided the precipitation, temperatures and evapo-transpiration fields used for the impact analysis. Based on downscaled climate projections, 3 reference scenarios for the period 2071-2100 (i.e. the driest, the wettest and the mild year) were selected and used to run a regional geomorphoclimatic and hydrogeological model. The final output of the model ensemble produced information about the potential variations of the water balance components (e.g. river discharge, groundwater level and volume) due to climate change. Such projections were used to develop potential hazard scenarios for the case study area, to be further applied within climate change risk assessment studies for groundwater resources and associated ecosystems. This paper describes the models' chain and the methodological approach adopted in the TRUST project and analyzes the hazard scenarios produced in order to investigate climate change risks for the case study area.

Climate change impact assessment in Veneto and Friuli Plain groundwater. Part II: a spatially resolved regional risk assessment.

Climate change impact assessment on water resources has received high international attention over the last two decades, due to the observed global warming and its consequences at the global to local scale. In particular, climate-related risks for groundwater and related ecosystems pose a great concern to scientists and water authorities involved in the protection of these valuable resources. The close link of global warming with water cycle alterations encourages research to deepen current knowledge on relationships between climate trends and status of water systems, and to develop predictive tools for their sustainable management, copying with key principles of EU water policy. Within the European project Life+ TRUST (Tool for Regional-scale assessment of groundwater Storage improvement in adaptation to climaTe change), a Regional Risk Assessment (RRA) methodology was developed in order to identify impacts from climate change on groundwater and associated ecosystems (e.g. surface waters, agricultural areas, natural environments) and to rank areas and receptors at risk in the high and middle Veneto and Friuli Plain (Italy). Based on an integrated analysis of impacts, vulnerability and risks linked to climate change at the regional scale, a RRA framework complying with the Sources-Pathway-Receptor-Consequence (SPRC) approach was defined. Relevant impacts on groundwater and surface waters (i.e. groundwater level variations, changes in nitrate infiltration processes, changes in water availability for irrigation) were selected and analyzed through hazard scenario, exposure, susceptibility and risk assessment. The RRA methodology used hazard scenarios constructed through global and high resolution model simulations for the 2071-2100 period, according to IPCC A1B emission scenario in order to produce useful indications for future risk prioritization and to support the addressing of adaptation measures, primarily Managed Artificial Recharge (MAR) techniques. Relevant outcomes from the described RRA application highlighted that potential climate change impacts will occur with different extension and magnitude in the case study area. Particularly, qualitative and quantitative impacts on groundwater will occur with more severe consequences in the wettest and in the driest scenario (respectively). Moreover, such impacts will likely have little direct effects on related ecosystems - croplands, forests and natural environments - lying along the spring area (about 12% of croplands and 2% of natural environments at risk) while more severe consequences will indirectly occur on natural and anthropic systems through the reduction in quality and quantity of water availability for agricultural and other uses (about 80% of agricultural areas and 27% of groundwater bodies at risk).

Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway.

The positive effect of adult undifferentiated mesenchymal stem cells (MSCs) on neuronal survival has already been reported, although the mechanisms by which MSCs exert their effect are still a matter of debate. Here we have demonstrated that MSCs are able to prolong the survival of dorsal root ganglion (DRG) neurons mainly by inhibiting some proteolytic enzymes, and in particular the pathway of metalloproteinases (MMPs), a family of proteins that are involved in many neuronal processes, including survival. The inhibition of MMPs was both direct, by acting on MT-MMP1, and indirect, by acting on those proteins that regulate MMPs' activation, such as Timp-1 and Sparc. The importance of the MMPs' down-regulation for neuronal survival was also demonstrated by using N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycyl hydroxamic acid (NNGH), a wide range inhibitor of metalloproteinases, which was able to increase the survival of DRG neurons in a significant manner. The down-regulation of MMPs, obtained both by MSC contact and by chemical inhibition, led to the inactivation of caspase 3, the executor of apoptotic death in DRG neurons cultured alone, while caspase 7 was found to be irrelevant for the apoptotic process. The capacity of MSCs to prevent apoptosis mainly by inactivating the metalloproteinase pathway is an important finding that sheds light on MSCs' mechanism of action, making undifferentiated MSCs a promising tool for the treatment of many different neurodegenerative pathologies.

Human cholangiocarcinoma development is associated with dysregulation of opioidergic modulation of cholangiocyte growth.

BACKGROUND/AIMS: Incidence of cholangiocarcinoma is increasing worldwide, yet remaining highly aggressive and with poor prognosis. The mechanisms that drive cholangiocyte transition towards malignant phenotype are obscure. Cholangiocyte benign proliferation is subjected to a self-limiting mechanism based on the autocrine release of endogenous opioid peptides. Despite the presence of both, ligands interact with delta opioid receptor (OR), but not with microOR, with the consequent inhibition of cell growth. We aimed to verify whether cholangiocarcinoma growth is associated with failure of opioidergic regulation of growth control. METHODS: We evaluated the effects of OR selective agonists on cholangiocarcinoma cell proliferation, migration and apoptosis. Intracellular signals were also characterised. RESULTS: Activation of microOR, but not deltaOR, increases cholangiocarcinoma cell growth. Such an effect is mediated by ERK1/2, PI3K and Ca(2+)-CamKIIalpha cascades, but not by cAMP/PKA and PKCalpha. microOR activation also enhances cholangiocarcinoma cell migration and reduces death by apoptosis. The anti-apoptotic effect of microOR was PI3K dependent. CONCLUSIONS: Our data indicate that cholangiocarcinoma growth is associated with altered opioidergic regulation of cholangiocyte biology, thus opening new scenarios for future surveillance or early diagnostic strategies for cholangiocarcinoma.

Effectiveness of oral hygiene protocol in patients with post-traumatic splinting.

AIM: In dental trauma with severe periodontal tissue involvement, as dental avulsion and severe luxation, the splinting procedure requires the patient to maintain a scrupulous hygiene of the affected zone, so to allow an effective tissue healing. The aim of this study was to assess the effectiveness of a specific oral hygiene protocol in the treatment of patients with post-traumatic splinting, comparing the plaque indexes of dental hygienist-helped patients versus not helped. MATERIALS AND METHODS: This study was carried out on 82 selected patients with post-traumatic splinting due to traumatic avulsion and severe luxation. They were divided into 2 groups, comparable for age, sex, type of trauma and splinting. The group A patients underwent an oral hygiene protocol, managed by a dental hygienist, while the group B patients were followed without the help of the hygienist. Plaque indexes were observed and compared in all cases during 6 weeks-follow up. RESULTS: Our results showed that at the 6th week follow up the plaque indexes of dental hygienist-assisted traumatized patients were significantly (p=0.001) lower than those of not assisted patients. CONCLUSION: Therefore, the role of dental hygienists is essential in the management of dental trauma with periodontal damage, which needs specific oral hygiene protocols.

Surgical removal and immediate reattachment of coronal fragment embedded in lip.

This case describes a patient with a traumatic crown fracture of an upper incisor, associated with a laceration wound in the lower lip, showing local oedema. While palpating the tissues of the lower lip we felt the presence of a foreign body. This was confirmed by a radiograph of the lip that showed a radiopaque material, being similar to the coronal fragment of the fractured incisor. It was successfully surgically removed and immediately reattached using a composite adhesive technique. At the follow-up of 1 year later the vitality test on the teeth was positive and neither one of the two traumatized teeth showed any sign of discoloration.

Root resorption in dental trauma: 45 cases followed for 5 years.

We aimed to: (i) study the prevalence of root resorption after luxation or avulsion injuries on permanent teeth referred to our dental clinic over a 3-year period; (ii) study the relationship between type of injury and resultant type of resorption complication; and (iii) evaluate success of treatment protocols for various resorption complications. We observed 1943 patients with dental trauma, aged between 2 and 26 years, referred to the Accident and Emergency Department of the Dental Clinic, University of Brescia, from 1st September 1997 to 31st December 2001. Of these, 261 permanent teeth had sustained luxation (n = 188) or avulsion (n = 73) injuries. Permanent teeth luxation and avulsion injuries occurred most often in upper incisors (75%) of patients mostly aged 12-21 years, with males more commonly affected than females (68.3% vs. 31.7%). These cases were followed for 5 years, and complications and response to treatment were recorded. Root resorption was observed in 45 (17.24%) of these cases. Of the 45 cases with resorption, 9 were associated with luxation injury (20%) while 36 (80%) with avulsion. We distinguished 30 cases of inflammatory root resorption (18 transient and 12 progressive) and 15 cases of ankylosis and osseous replacement. When resorption was recognized, quick and effective treatment could still result in an excellent functional and aesthetic outcome for these teeth.

Clinical and epidemiological study of traumatic root fractures.

The aim of this work was to study the prevalence and clinical presentation of root fractures in a series of patients with dental trauma. Treatment strategies were classified and outcomes after a 6-month period presented. The study population comprised 76 patients (between the ages of 2 and 55 years) with 93 root fractures in their teeth (18 primary, 75 permanent). Data were collected following the taking of a detailed clinical history, objective clinical examination and photographic and radiological investigation. Since most of the primary teeth were extracted, only cases with root fracture of permanent teeth were followed-up: in all, 24 patients with 31 teeth with root fractures. The prevalence of root fractures in permanent teeth was 7.7% of all injuries, while in primary teeth it was 3.8%. The most frequently involved teeth were the maxillary incisors with a percentage of 75% in permanent teeth. Moreover, 40% of root fractures in permanent teeth were associated with fracture of the alveolar bone and of the soft tissues and in 45% of cases, the adjacent teeth were also injured. The results of this study reaffirm the necessity for scrupulous diagnosis of teeth after a traumatic injury. Adjacent teeth and those in the opposing arch should not be ignored. Treatment is multidisciplinary, requiring surgical, orthodontic, operative and prosthetic compliance. Periodic check-up is essential.