The dynamic sagittal balance: Definition of dynamic spino-pelvic parameters using a method based on gait analysis.

Introduction: Evaluation of sagittal balance parameters is a standard assessment before spine surgery. However, these parameters can change during walking. We aimed to describe the behavior of spino-pelvic parameters during walking in healthy subjects. Material and methods: Analyses were performed in 60 healthy subjects. Static spinal sagittal balance parameters were assessed. We performed gait analysis and we used SMART-DX 500® to analyze parameters aimed at defining dynamic sagittal balance, including pelvic tilt angle (PTA), sagittal trunk shift (STS), and trunk angle (TA). We considered rotational and obliquity movements of the pelvis, flexo-extension movements of the hip, trunk, and knees. Analyses were performed in a standing posture and during walking. Results: PTA-cycle, PTA-stance, PTA-swing, STS-cycle, STS-stance, and STS-swing showed good-to-excellent internal reliability (ICC = 0.867; ICC = 0.700; ICC = 0.817, respectively). The parameters with the lowest variability were radiographic PI (CV = 16.53%), PTA-stance (CV = 9.55%), and PTA-swing (CV = 17.22%). PT was directly related to PTA-cycle (r = 0.534, p = .027). PI was inversely correlated with trunk flexo-extension range of motion (r = -0.654, p = .004) and dynamic PT (r = -0.489, p = .047). LL and SS were directly related to knee flexo-extension (r = 0.505, p = .039; r = 0.493, p = .045, respectively). SVA was correlated with the trunk obliquity in dynamics (r = 0.529, p = .029). PTA-cycle was directly related to trunk obliquity (r = 0.538, p = .049). STS and TA in the three phases of step were related to the kinematic parameters of the pelvis. TA was related to flexo-extension of the hip and knee. Conclusions: Variations of dynamic spino-pelvic parameters occur during walking and modify sagittal balance from a static to a dynamic condition.

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.

Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.

Subchronic memantine induced concurrent functional disconnectivity and altered ultra-structural tissue integrity in the rodent brain: revealed by multimodal MRI.

BACKGROUND: An effective NMDA antagonist imaging model may find key utility in advancing schizophrenia drug discovery research. We investigated effects of subchronic treatment with the NMDA antagonist memantine by using behavioural observation and multimodal MRI. METHODS: Pharmacological MRI (phMRI) was used to map the neuroanatomical binding sites of memantine after acute and subchronic treatment. Resting state fMRI (rs-fMRI) and diffusion MRI were used to study the changes in functional connectivity (FC) and ultra-structural tissue integrity before and after subchronic memantine treatment. Further corroborating behavioural evidences were documented. RESULTS: Dose-dependent phMRI activation was observed in the prelimbic cortex following acute doses of memantine. Subchronic treatment revealed significant effects in the hippocampus, cingulate, prelimbic and retrosplenial cortices. Decreases in FC amongst the hippocampal and frontal cortical structures (prelimbic, cingulate) were apparent through rs-fMRI investigation, indicating a loss of connectivity. Diffusion kurtosis MRI showed decreases in fractional anisotropy and mean diffusivity changes, suggesting ultra-structural changes in the hippocampus and cingulate cortex. Limited behavioural assessment suggested that memantine induced behavioural effects comparable to other NMDA antagonists as measured by locomotor hyperactivity and that the effects could be reversed by antipsychotic drugs. CONCLUSION: Our findings substantiate the hypothesis that repeated NMDA receptor blockade with nonspecific, noncompetitive NMDA antagonists may lead to functional and ultra-structural alterations, particularly in the hippocampus and cingulate cortex. These changes may underlie the behavioural effects. Furthermore, the present findings underscore the utility and the translational potential of multimodal MR imaging and acute/subchronic memantine model in the search for novel disease-modifying treatments for schizophrenia.

Role of immediate-release morphine (MIR) in the treatment of predictable pain in radiotherapy.

Radiotherapy is crucial in the management of cancer patients in both the curative and palliative settings. However, patients often report pain both during positioning for, and execution of, radiotherapy and this may be a reason for interrupting the radiotherapy session. This observation is common even if the patient is undergoing baseline drug therapy for cancer pain. Recent data suggest that orally administrated immediate-release morphine (MIR) is able to reduce pain in patients with predictable pain. The authors tested a rescue dose of MIR 10 or 20 mg, 20 to 60 minutes before radiotherapy, to verify the effectiveness of MIR in this setting and also to assess the patient's ability to receive the full course of radiotherapy. One hundred forty consecutive patients were evaluated during radiotherapy treatment and visual analogue scale (VAS) and positioning VAS scores were assessed. All patients completed the course of scheduled radiotherapy and pain was well controlled, despite the fact that previous pharmacological treatment had not been able to completely control chronic cancer pain. These data strongly suggest a role for MIR pretreatment in patients with pain due to positioning during radiotherapy.

Life cycle assessment for optimising the level of separated collection in integrated MSW management systems.

This life cycle assessment study analyses material and energy recovery within integrated municipal solid waste (MSW) management systems, and, in particular, the recovery of the source-separated materials (packaging and organic waste) and the energy recovery from the residual waste. The recovery of materials and energy are analysed together, with the final aim to evaluate possible optimum levels of source-separated collection that lead to the most favourable energetic and environmental results; this method allows identification of an optimum configuration of the MSW management system. The results show that the optimum level of source-separated collection is about 60%, when all the materials are recovered with high efficiency; it decreases to about 50%, when the 60% level is reached as a result of a very high recovery efficiency for organic fractions at the expense of the packaging materials, or when this implies an appreciable reduction of the quality of collected materials. The optimum MSW management system is thus characterized by source-separated collection levels as included in the above indicated range, with subsequent recycling of the separated materials and energy recovery of the residual waste in a large-scale incinerator operating in combined heat and power mode.

Primary and secondary components of PM2.5 in Milan (Italy).

In sampling campaigns--carried out by means of a high-volume gravimetric sampler--performed between August 2002 and December 2003, 24-h PM2.5 samples have been collected at an urban background site in downtown Milan and analyzed for elemental and organic carbon, ionic species (i.e., chloride, nitrates, sulfates and ammonium) and some elemental species. Chemical speciation data are evaluated also in terms of primary and secondary components of fine particulate matter: in particular, the contribution of secondary organic aerosols (SOA) and of the primary contribution from traffic to observed PM2.5 concentration levels are evaluated by means of the EC tracer method.

Energy recovery from municipal waste: a case study for a middle-sized Italian district.

This paper reports the main outcome of research to compare and assess the merits of alternative strategies for energy recovery from municipal solid waste downstream of material recovery for an Italian province. Strategies analysed are based on well-established combustion technologies available at the commercial scale in the Italian market in comparison with an innovative but not yet proven option of refuse derived fuel gasification and subsequent co-combustion of syngas in a combined cycle power plant. The comparison is made using mass and energy balances, environmental assessment and economic analysis. From an energetic point of view, the best strategy is the one based on the refuse derived fuel gasification, which, on the contrary, does not show interesting environmental results. In this perspective, the best results are from strategies based on a dedicated plant, particularly when unsorted residual waste collected downstream of material recovery is used. Finally, from an economic point of view, the strategy with gasification allows the highest revenues from the sale of energy.

Real-time closed-loop electrophysiology: towards new frontiers in in vitro investigations in the neurosciences.

Reflected at any level of organization of the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most in vitro preparations and experimental protocols operate autonomously, and do not depend on the output of the studied system. Thanks to the progress in digital signal processing and real-time computing, it is now possible to artificially close the loop and investigate biophysical processes and mechanisms under increased realism. In this contribution, we review some of the most relevant examples of a new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to multi-electrode distributed feedback stimulation. We are convinced these represents the beginning of new frontiers for the in vitro investigation of the brain, promising to open the still existing borders between theoretical and experimental approaches while taking advantage of cutting edge technologies.

Health risk analysis of PCDD/F emissions from MSW incineration: comparison of probabilistic and deterministic approaches.

Incremental lifetime health risks due to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emitted from municipal waste incineration (MSWI) facilities were evaluated for resident population in the area of the plant. Risk assessment was performed through a multipathway combined probabilistic/deterministic approach for analyzing the effects of uncertainty and intrinsic variability of the main PCDD/F emission related parameters on final predicted values. Exposure through direct inhalation of contaminated air, soil ingestion, soil dermal contact and diet were considered, with the propagation of the variability of input parameters throughout the evaluation performed with Monte Carlo simulation techniques. The application to a case study representative of two different technological scenarios (modern facilities equipped with BAT - Best Available Technology - and older incinerators) in a location site typical of Northern Italy situation results in median values of the maximum individual excess risk on the order of 10(-9) and 10(-7) for most recent and older plant configurations, respectively. Corresponding ratios for the 90th and 10th percentile values are around 7 and 9. Individual risk estimates derived for the same scenarios from conventional deterministic approaches, where large conservative assumptions are normally adopted for compensating the lack of knowledge about uncertainty, are essentially comparable with maximum values resulting from the probabilistic approach, thus leading to situations with extreme and very low probabilities of occurrence. PCDD/F health risks from MSWI emissions might thus result largely overestimated if real emission characteristics are not properly considered in the assessment procedure. Sensitivity analysis for identifying the contribution of different input parameters on final predicted risk variance indicates, for the area considered in the simulation, a prevailing influence of PCDD/F stack concentration, with exposures arising from soil deposition phenomena substantially negligible: this latter result further points out the requirements for a very careful identification of base input data values for PCDD/F stack concentrations, at least for those situations where plants are located nearby urban areas.

Transient rhythmic network activity in the somatosensory cortex evoked by distributed input in vitro.

The initiation and maintenance of physiological and pathophysiological oscillatory activity depends on the synaptic interactions within neuronal networks. We studied the mechanisms underlying evoked transient network oscillation in acute slices of the adolescent rat somatosensory cortex and modeled its underpinning mechanisms. Oscillations were evoked by brief spatially distributed noisy extracellular stimulation, delivered via bipolar electrodes. Evoked transient network oscillation was detected with multi-neuron patch-clamp recordings under different pharmacological conditions. The observed oscillations are in the frequency range of 2-5 Hz and consist of 4-12 mV large, 40-150 ms wide compound synaptic events with rare overlying action potentials. This evoked transient network oscillation is only weakly expressed in the somatosensory cortex and requires increased [K+]o of 6.25 mM and decreased [Ca2+]o of 1.5 mM and [Mg2+]o of 0.5 mM. A peak in the cross-correlation among membrane potential in layers II/III, IV and V neurons reflects the underlying network-driven basis of the evoked transient network oscillation. The initiation of the evoked transient network oscillation is accompanied by an increased [K+]o and can be prevented by the K+ channel blocker quinidine. In addition, a shift of the chloride reversal potential takes place during stimulation, resulting in a depolarizing type A GABA (GABAA) receptor response. Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), N-methyl-D-aspartate (NMDA), or GABA(A) receptors as well as gap junctions prevents evoked transient network oscillation while a reduction of AMPA or GABA(A) receptor desensitization increases its duration and amplitude. The apparent reversal potential of -27 mV of the evoked transient network oscillation, its pharmacological profile, as well as the modeling results suggest a mixed contribution of glutamatergic, excitatory GABAergic, and gap junctional conductances in initiation and maintenance of this oscillatory activity. With these properties, evoked transient network oscillation resembles epileptic afterdischarges more than any other form of physiological or pathophysiological neocortical oscillatory activity.

Alternative strategies for energy recovery from municipal solid waste Part A: Mass and energy balances.

This two-part paper assesses four strategies for energy recovery from municipal solid waste (MSW) by dedicated waste-to-energy (WTE) plants generating electricity through a steam cycle. The feedstock is the residue after materials recovery (MR), assumed to be 35% by weight of the collected MSW. In strategy 1, the MR residue is fed directly to a grate combustor. In strategy 2, the MR residue is first subjected to light mechanical treatment. In strategies 3 and 4, the MR residue is converted into RDF, which is combusted in a fluidized bed combustor. To examine the relevance of scale, we considered a small waste management system (WMS) serving 200,000 people and a large WMS serving 1,200,000 people. A variation of strategy 1 shows the potential of cogeneration with district heating. The assessment is carried out by a Life Cycle Analysis where the electricity generated by the WTE plant displaces electricity generated by fossil fuel-fired steam plants. Part A focuses on mass and energy balances, while Part B focuses on emissions and costs. Results show that treating the MR residue ahead of the WTE plant reduces energy recovery. The largest energy savings are achieved by combusting the MR residue "as is" in large scale plants; with cogeneration, primary energy savings can reach 2.5% of total societal energy use.

Alternative strategies for energy recovery from municipal solid waste Part B: Emission and cost estimates.

This two-part paper assesses four strategies for energy recovery from Municipal Solid Waste (MSW) by dedicated Waste-To-Energy (WTE) plants. In strategy 1, the residue of Material Recovery (MR) is fed directly to a grate combustor, while in strategy 2 the grate combustor comes downstream of light mechanical treatment. In strategies 3 and 4, the MR residue is converted into Refuse Derived Fuel (RDF), in a fluidized cumbuster bed. The results of Part A, devoted to mass and energy balances, clearly show that pre-treating the MR residue in order to increase the heating value of the feedstock fed to the WTE plant has marginal effects on the energy efficiency of the WTE plant. When considering the efficiency of the whole strategy of waste management, the energy balances show that the more thorough the pre-treatment, the smaller the amount of energy recovered per unit of MR residue. Starting from the heat/mass balances illustrated in Part A, Part B examines the environmental impacts and economics of the various strategies by means of a Life Cycle Assessment (LCA). Results show that treating the MR residues ahead of the WTE plant does not provide environmental or economic benefits. RDF production worsens almost all impact indicators because it reduces net electricity production and thus the displacement of power plant emissions; it also increases costs, because the benefits of improving the quality of the material fed to the WTE plant do not compensate the cost of such improvement.

Single-neuron discharge properties and network activity in dissociated cultures of neocortex.

Cultures of neurons from rat neocortex exhibit spontaneous, temporally patterned, network activity. Such a distributed activity in vitro constitutes a possible framework for combining theoretical and experimental approaches, linking the single-neuron discharge properties to network phenomena. In this work, we addressed the issue of closing the loop, from the identification of the single-cell discharge properties to the prediction of collective network phenomena. Thus, we compared these predictions with the spontaneously emerging network activity in vitro, detected by substrate arrays of microelectrodes. Therefore, we characterized the single-cell discharge properties to Gauss-distributed noisy currents, under pharmacological blockade of the synaptic transmission. Such stochastic currents emulate a realistic input from the network. The mean (m) and variance (s(2)) of the injected current were varied independently, reminiscent of the extended mean-field description of a variety of possible presynaptic network organizations and mean activity levels, and the neuronal response was evaluated in terms of the steady-state mean firing rate (f). Experimental current-to-spike-rate responses f(m, s(2)) were similar to those of neurons in brain slices, and could be quantitatively described by leaky integrate-and-fire (IF) point neurons. The identified model parameters were then used in numerical simulations of a network of IF neurons. Such a network reproduced a collective activity, matching the spontaneous irregular population bursting, observed in cultured networks. We finally interpret such a collective activity and its link with model details by the mean-field theory. We conclude that the IF model is an adequate minimal description of synaptic integration and neuronal excitability, when collective network activities are considered in vitro.

The flux and mass balance of PCDD/F in a MSW incineration full scale plant.

PCDD/F are one of the most significant environmental concerns of municipal solid waste disposal through incineration processes. With the main purpose of evaluating their presence along the flue gas line and establishing a mass balance over the whole system, an extensive research study was performed on a full scale plant. Present paper reports the main results obtained, with particular reference to the PCDD/F concentration profiles and mass balance in the post-furnace region. where significant formation of these compounds might take place. PCDD/F mass fluxes evaluated in all the residues arising from the process are also reported.

Evaluation of cardiac and respiratory involvement in sarcoglycanopathies.

Sarcoglycanopathies constitute a subgroup of limb-girdle recessive muscular dystrophies due to defects in sarcoglycan complex that comprises five distinct transmembrane proteins called alpha-, beta-, gamma-, delta-and epsilon-sarcoglycans. As it is well known that sarcoglycans are expressed both in heart and in skeletal muscles and a complete deficiency in delta-sarcoglycan is the cause of the Syrian hamster BIO.14 cardiomyopathy, we studied cardiac and respiratory involvement in 20 patients with sarcoglycanopathies by clinical, electrocardiographic, echocardiographic, scintigraphic and spirometric assessments. A normal heart function was found in 31.3% of all patients; a preclinical cardiomyopathy in 43.7%; an arrhythmogenic cardiomyopathy in 6.3% and initial signs of dilated cardiomyopathy in 18.7%. In one patient the data were examined retrospectively. No correlation was found between cardiac and skeletal muscle involvement. With reference to the type of sarcoglycanopathy, signs of hypoxic myocardial damage occurred in beta-, gamma- and delta-sarcoglycanopathies, while initial signs of a dilated cardiomyopathy in gamma- and delta-sarcoglycanopathies were found. A normal respiratory function was observed in 23.5% of all patients, a mild impairment in 35.4%, a moderate impairment in 29.4%, and a severe impairment in 11.7%.

Insulin release at the molecular level: metabolic-electrophysiological modeling of the pancreatic beta-cells.

The role of pancreatic beta-cells is fundamental in the control endocrine system, maintaining the blood glucose homeostais in a physiological regime, via the glucose-induced release of insulin. An increasing amount of detailed experimental evidences at the cellular and molecular biology levels have been collected on the key factors determining the insulin release by the pancreatic beta-cells. The direct transposition of such experimental data into accurate mathematical descriptions might contribute to considerably clarify the impact of each cellular component on the global glucose metabolism. Under these perspectives, we model and computer-simulate the stimulus-secretion coupling in beta-cells by describing four interacting cellular subsystems, consisting in the glucose transport and metabolism, the excitable electrophysiological behavior, the dynamics of the intracellular calcium ions, and the exocytosis of granules containing insulin. We explicit the molecular nature of each subsystem, expressing the mutual relationships and the feedbacks that determine the metabolic-electrophysiological behavior of an isolated beta-cell. Finally, we discuss the simulation results of the behavior of isolated beta-cells as well as of population of electrically coupled beta-cells in Langerhans islets, under physiological and pathological conditions, including noninsulin-dependent diabetes mellitus (NIDDM) and hyperinsulinemic hypoglycaemia (PHHI).

Synthesis of generalized algorithms for the fast computation of synaptic conductances with Markov kinetic models in large network simulations.

Markovkinetic models constitute a powerful framework to analyze patch-clamp data from single-channel recordings and model the dynamics of ion conductances and synaptic transmission between neurons. In particular, the accurate simulation of a large number of synaptic inputs in wide-scale network models may result in a computationally highly demanding process. We present a generalized consolidating algorithm to simulate efficiently a large number of synaptic inputs of the same kind (excitatory or inhibitory), converging on an isopotential compartment, independently modeling each synaptic current by a generic n-state Markov model characterized by piece-wise constant transition probabilities. We extend our findings to a class of simplified phenomenological descriptions of synaptic transmission that incorporate higher-order dynamics, such as short-term facilitation, depression, and synaptic plasticity.

Activity-driven computational strategies of a dynamically regulated integrate-and-fire model neuron.

Activity-dependent slow biochemical regulation processes, affecting intrinsic properties of a neuron, might play an important role in determining information processing strategies in the nervous system. We introduce second-order biochemical phenomena into a linear leaky integrate-and-fire model neuron together with a detailed kinetic description for synaptic signal transduction. In this framework, we investigate the membrane intrinsic electrical properties differentiation, showing the appearance of activity-dependent shifts between integration and temporal coincidence detection operating mode, for the single unit of a network.

Fast calculation of short-term depressing synaptic conductances.

An efficient implementation of synaptic transmission models in realistic network simulations is an important theme of computational neuroscience. The amount of CPU time required to simulate synaptic interactions can increase as the square of the number of units of such networks, depending on the connectivity convergence. As a consequence, any realistic description of synaptic phenomena, incorporating biophysical details, is computationally highly demanding. We present a consolidating algorithm based on a biophysical extended model of ligand-gated postsynaptic channels, describing short-term plasticity such as synaptic depression. The considerable speed-up of simulation times makes this algorithm suitable for investigating emergent collective effects of short-term depression in large-scale networks of model neurons.