Short bent-core molecules: X-ray, polarization, dielectricity, texture and electro-optics investigations.

Bent-core liquid crystals based on 1,2,4-oxadiazole as a central unit have been the first mesogens to exhibit a ferroelectric response in the nematic phase. This behavior has been widely recognized as due to the presence of smectic-like polar cybotactic clusters permeating the nematic phase. Unfortunately, these compounds exhibited rather high melting points, about 120 °C, due to the presence of four benzene rings in the molecules. Here we describe the synthesis and physical characterization of a new series of BC mesogens, featuring the same bent core as the previous compounds but shorter outer substituents. By keeping only two benzene rings, we were able to lower the melting points to about 70 °C. However, while X-ray diffraction and dielectric spectroscopy measurements confirm the cybotactic nature of the nematic phase of these compounds, polarization and electro-optical measurements ascribe their polar response to flexoelectricity rather than to spontaneous polarization. Finally, texture investigation suggests the biaxiality of the nematic phase, which is indicated also by conoscopic measurements. These results are important for recognizing size and rigidity limitations in designing bent-core liquid crystal molecules suitable for applications.

Technological quality of dough and breads from commercial algarroba-wheat flour blends.

Algarroba flour is used to supplement lysine-limiting systems such as wheat flour due to its amino acidic composition. The effects of adding up to 30% of this flour to wheat flour (W-A30) on dough characteristics and breadmaking performance were studied. Dough rheology was tested by farinograph, oscillatory rheometry and texture profile analyses. Molecular mobility was evaluated by nuclear magnetic resonance, and thermal properties were analyzed by differential scanning calorimetry and viscoamylograph studies. Besides, different bread quality parameters were evaluated. Incorporation of algarroba flour resulted into increase in water absorption, development time and degree of softening, and decrease in stability of wheat flour, leading to softer, less adhesive and elastic dough, although at intermediate replacement levels cohesiveness improved. At the molecular level, a reduction of water activity and limited proton motion were observed in W-A30 samples, suggesting that protons were highly bound to the dough matrix. Dough samples with algarroba flour showed lower G' and G″ values than the control, although with the formation of a more elastic structure for W-A30. In addition, algarroba flour produced a protective effect on starch granule disruption and interfered with amylose-amylose association during cooling. The specific volume of breads decreased with the increase in algarroba level, W-A30 reaching the highest decrease (15%). Bread crumbs with algarroba flour exhibited higher values of hardness and resilience. The use of algarroba flour resulted in lower quality when compared to the control. However, algarroba flour at 20% level can be added to wheat flour to obtain bakery products of similar technological quality and with improved nutritional components.

Acute effects of simultaneous electromyostimulation and vibration on leg blood flow in spinal cord injury.

STUDY DESIGN: Randomized crossover. OBJECTIVES: To analyze the acute effects of isolated and simultaneous application of whole-body vibration (WBV) and electromyostimulation (ES) on popliteal artery blood velocity (BV) and skin temperature (ST) of the calf in subjects with spinal cord injury (SCI). SETTING: Valladolid, Spain. METHODS: Ten subjects with SCI were assessed in five different sessions. After a familiarization session, four interventions were applied in random order; WBV, ES, simultaneous WBV and ES (WBV+ES), and 30 s of WBV followed by 30 s of ES (WBV30/ES30). Each intervention consisted of 10 sets × 1 min ON+1 min OFF. Subjects were seated on their own wheelchairs with their feet on the vibration platform (10 Hz, 5 mm peak-to-peak), and ES was applied on the gastrocnemius muscle of both legs (8 Hz, 400 µs). RESULTS: The simultaneous application (WBV+ES) produced the greatest increase in mean BV (MBV; 36% and 42%, respectively) and peak BV (PBV; 30% and 36%, respectively) during the intervention. This intervention produced the greatest mean increases in MBV (21%) and PBV (19%) during the recovery period. Last, this intervention produced the highest increase in ST during the intervention (2.1 °C). CONCLUSION: The simultaneous application of WBV+ES seems to produce a greater increase in MBV and PBV of the popliteal artery and ST of the calf than the isolated (WBV or ES) or consecutive application of both stimuli (WBV30/ES30). This study provides an efficient therapeutic methodology to improve peripheral arterial properties, which is pivotal in SCI patient's rehabilitation.

Chronic effects of simultaneous electromyostimulation and vibration on leg blood flow in spinal cord injury.

STUDY DESIGN: Randomized two-group parallel. OBJECTIVES: The objective of this study was to analyze the adaptations on the popliteal artery (mean blood velocity (MBV), peak blood velocity (PBV), arterial resting diameter (RD) and blood flow (BF)) induced by 12 weeks of simultaneous application of whole-body vibration and electromyostimulation (WBV+ES) in patients with spinal cord injury (SCI). Secondarily, the musculoskeletal effects of this therapy on the gastrocnemius muscle thickness (MT) and femoral neck bone mineral density (BMD) were analyzed. SETTING: Valladolid, Spain. METHODS: Seventeen SCI patients (American Spinal Injury Association (ASIA) A or B) were randomly assigned to the experimental group (EG=9) or the control group (CG=8). Each subject was assessed in four different occasions: at baseline, after 6 weeks (Post-6) and 12 weeks of the treatment (Post-12) and 8 weeks after the end of the treatment (Post-20). Subjects in the EG performed 30 10-min sessions of WBV+ES during 12 weeks. RESULTS: In the EG, RD increased compared with the baseline value at Post-6 (9.5%, P<0.01), Post-12 (19.0%, P<0.001) and Post-20 (16.7%, P<0.001). Similarly, in the EG, BF increased compared with the baseline value and with CG only at Post-12 ((33.9%, P<0.01) and (72.5%, P<0.05), respectively). Similarly, WBV+ES increased the MT of the gastrocnemius. BMD of both hips remained invariable during the study. CG showed no change at any point. CONCLUSIONS: WBV+ES improved popliteal artery BF, RD and MT after 12 weeks in SCI patients. This increase in RD remained above baseline after 8 weeks. The combination of WBV and ES could be considered a promising alternative to reverse the musculoskeletal atrophy and improve peripheral vascular properties in SCI patients.

Where do we stand with IPF treatment?

Despite receiving 'weak no' recommendations in the updated guidelines on treating patients with Idiopathic Pulmonary Fibrosis (IPF), two key treatment options are pirfenidone and N-acetylcysteine (NAC), and both are used in clinical practice. The efficacy of pirfenidone is supported by a number of Phase III trials as well as a Cochrane meta-analysis. Tolerability data are also provided by clinical trials and a long-term extension phase of these studies. Pirfenidone is approved in Europe for the treatment of patients with mild-to-moderate IPF. NAC-based therapy has no such approval, but is commonly used to treat patients. A Phase III trial suggested some benefit of the NAC, prednisone and azathioprine regimen for IPF patients, but the study had many limitations. A further study to investigate this regimen, compared with a placebo alone arm, was recently stopped due to increased mortality in the triple-therapy arm. Discussion of these data and recent findings highlight the importance of a further update to the existing guidelines, so that IPF specialists can provide the most up-to-date advice and treatment to patients in clinical practice.

Muscular adaptations after two different volumes of blood flow-restricted training.

This study aimed to gain an insight into the adaptations of muscle strength and skeletal muscle thickness after two different volumes of blood flow restriction training (BFRT), and compare them with high-intensity training. The sample was divided into four groups: low-volume, low-intensity BFRT (BFRT LV); high-volume, low-intensity BFRT (BFRT HV); traditional high-intensity resistance training (HIT); and a control group, which maintained their routine activities (CON). Leg extension one repetition maximum (1RM), isokinetic peak knee extension, and flexion torques at 60°/s and 180°/s as well as muscle thickness of the rectus femoris (RF) and vastus lateralis (VL) were assessed at baseline and after 5 weeks of training BFRT LV (7.03%, P < 0.05), BFRT HV (6.24%, P < 0.05) and HIT (18.86%, P < 0.001) groups increased 1RM performance, while no changes were observed in the CON group. Muscle thickness of the RF and VL was increased irrespective of the training group (7.5%, P < 0.001; and 9.9%, P < 0.001, respectively). We conclude that doubling the exercise volume with BFRT causes no further benefit with muscular size or strength. Although similar increases in muscle thickness were observed between training groups, HIT increased 1RM performance to a greater extent compared to either volume of BFRT.

[Employment of disabled people regarding Italian Law "68/99": Florence's ASL N. 10 experience]. / Inserimento lavorativo dei soggetti disabili ai sensi della legge 68/99: l'esperienza della ASL10 di Firenze.

The reform of mandatory employment in Italy, performed by the national Law 68/99, represented a crucial step for the assertion of the right to work for disabled people. The aim of our experience is to obtain information about health and safety conditions of disabled people employed in targeted workplaces and about the issues for that workers keep or lose their job, possibly in order to take actions on workplaces and to improve job conditions for all other workers also. In this paper we used data regarding targeted employments of disabled people, collected during the year 2008 in the Province of Florence.

Simulation of dose deposition in stereotactic synchrotron radiation therapy: a fast approach combining Monte Carlo and deterministic algorithms.

A hybrid approach, combining deterministic and Monte Carlo (MC) calculations, is proposed to compute the distribution of dose deposited during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (i) the dose deposited by primary radiation (coming directly from the incident x-ray beam) is calculated in a deterministic way using ray casting techniques and energy-absorption coefficient tables and (ii) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining MC and deterministic calculations. In the MC part, a small number of particle histories are simulated. Every time a scattering or fluorescence event takes place, a splitting mechanism is applied, so that multiple secondary photons are generated with a reduced weight. The secondary events are further processed in a deterministic way, using ray casting techniques. The whole simulation, carried out within the framework of the Monte Carlo code Geant4, is shown to converge towards the same results as the full MC simulation. The speed of convergence is found to depend notably on the splitting multiplicity, which can easily be optimized. To assess the performance of the proposed algorithm, we compare it to state-of-the-art MC simulations, accelerated by the track length estimator technique (TLE), considering a clinically realistic test case. It is found that the hybrid approach is significantly faster than the MC/TLE method. The gain in speed in a test case was about 25 for a constant precision. Therefore, this method appears to be suitable for treatment planning applications.

Pressure dependence of the large-scale structure of water.

We report on small-angle x-ray scattering measurements on liquid water aimed at characterizing the pressure evolution of its large-scale structure. Diffraction profiles have been fitted assuming a Lorentzian dependence on the exchanged momentum. As a result, we observe an anomalous behavior of the diffracted intensity that tends to disappear, increasing either the pressure or the temperature. This effect is discussed in detail and imputed to the ability of hydrostatic pressure to weaken hydrogen bonds.

An analytical approach to estimating aberrations in curved multilayer optics for hard x-rays: 2. Interpretation and application to focusing experiments.

Aberration effects are studied in parabolic and elliptic multilayer mirrors for hard x-rays, basing on a simple analytical approach. The interpretation of the underlying equations provides insight into fundamental limitations of the focusing properties of curved multilayers. Using realistic values for the multilayer parameters the potential impact on the broadening of the focal spot is evaluated. Within the limits of this model, systematic contributions to the spot size can be described. The work is complemented by a comparison with experimental results obtained with a W/B(4)C curved multilayer mirror.

An analytical approach to estimating aberrations in curved multilayer optics for hard x-rays: 1. Derivation of caustic shapes.

An analytical approach has been developed to derive aberration effects in parabolic and elliptic multilayer optics with weak interaction between photons and matter. The method is based on geometrical ray tracing including refraction effects up to the first order of the refractive index decrement delta. In the parabolic case, the derivation leads to simple parametric equations for the caustic shape. In the elliptic case, the analytical results more involved, but can be well approximated by the parabolic solution. Both geometries are compared with regard to the fundamental impact on their focusing properties.

MRI activity and neutralising antibody as predictors of response to interferon beta treatment in multiple sclerosis.

OBJECTIVE: To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon beta treatment as response indicators in multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS were followed during the first 2 years of treatment. Neurological assessments were performed every 3 months or when a relapse was suspected. MRI scans performed at baseline and at 3, 4, 5 and 6 months after the start of treatment were assessed centrally for disease activity: new T2 or gadolinium enhancing T1 lesions. NAb were assessed using the MxA protein assay; positivity was defined as two consecutive titres >or=20 NU/ml. We evaluated the predictivity of an active scan, NAb positivity, or both, during the first 6 months of treatment, on the occurrence of clinical disease activity in the following 18 months. RESULTS: 147 patients were assessed at 16 centres. Predictivity parameters (with confidence intervals) were as follows: active scan, sensitivity (SN) 52% (34-69%), specificity (SP) 80% (65-91%), negative predictive value (NPV) 73% (58-77%), positive predictive value (PPV) 62% (42-79%), p = 0.002; NAb positivity, SN 71% (45-88%), SP 66% (55-76%), NPV 92% (82-97%), PPV 29% (16-45%), p = 0.01; active scan and NAb positivity, SN 71% (38-91%), SP 86% (73-94%), NPV 94% (86-98%), PPV 50% (29-70%), p = 0.0003. CONCLUSIONS: MRI activity and NAb occurrence during the first 6 months of interferon beta treatment were reliable predictors of long term clinical response, particularly when combined. Patients with negative predictors showed a less than 10% risk of developing clinical activity. Patients with positive predictors showed a 50% risk of further clinical activity. These patients need to be followed carefully with further MRI and NAb tests.

Structural characterization of the human cerebral myelin sheath by small angle x-ray scattering.

Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.

Drug release behaviour from methyl methacrylate-starch matrix tablets: effect of polymer moisture content.

The aim of this work was to study the effect of the initial moisture content of the polymer on the tabletting and drug release behaviour of controlled release inert matrices elaborated with methyl methacrylate (MMA)-starch copolymers. The copolymers, obtained by free radical polymerisation and dried by two different methods (oven-drying or freeze-drying), were equilibrated at different relative humidities (0%, 25%, 50% and 75% RH) at room temperature. From these copolymers, matrix systems were directly compressed containing either a slightly water-soluble drug (anhydrous theophylline) or a freely water-soluble drug (salbutamol sulphate), and their compaction properties and in vitro dissolution profiles were evaluated. The release profiles were compared following model-independent methods, such as the Qt parameter and the similarity factor f2. Moreover, several kinetic models were employed to evaluate the possible changes in the release mechanism. For anhydrous theophylline, the initial moisture content of the copolymers did not affect the release characteristics from the inert matrices under study, and a typical Fickian diffusion mechanism was observed for the different formulations. However, in case of salbutamol sulphate, the presence of moisture might induce a fast drug dissolution, promoting the weakness of the matrix structure and hence, its partial disintegration. So, an "anomalous" mixed phenomenon of diffusion and erosion was found, influenced by the initial moisture content of the copolymer.

Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers: effect of HPMC of different viscosity grades.

The aim of this paper is the modification of the release behaviour of hydrophilic HPMC-based matrices of different viscosity grade by the introduction of a new inert polymeric excipient hydroxypropylcellulose-methyl methacrylate (HCMMA). The drug released could be control by both mechanisms, the swelling rate from the hydrophilic matrices, and the porosity, tortuosity and water uptake capacity from inert matrices. The effects of drying methods, presence or absence of viscosity (HCMMA in relation with HPMC), proportion of two polymers and different viscosity grade of HPMC were studied. It was observed that the mixtures with FD-HCMMA needed less pressure, presented higher plasticity and their tablets were easier to obtain compared with OD-HCMMA mixtures. Only FD-HCMMA:K100M mixtures did not show any differences in the percentage of theophylline released when FD-HCMMA proportion changed (f2>95). All mixtures show double release mechanism, diffusion and erosion from the gel layer, but with higher contribution of the relaxation factor than on HPMC tablets. For the different mixtures HCMMA-HPMC, it is possible to see fronts movement profiles similar to swellable matrices. The results demonstrate that the use of high viscosity differences of HPMC or 50% HCMMA or above was required to produce modifications on theophylline monoaxial release modulation.

Soybean protein-based microparticles for oral delivery of probiotics with improved stability during storage and gut resistance.

The present work describes the encapsulation of probiotics using a by-product as wall material and a process feasible to be scaled-up: coacervation of soybean protein concentrate (SPC) by using calcium salts and spray-drying. SPC was extracted from soybean flour, produced during the processing of soybean milk, by alkaline extraction following isoelectric precipitation. Two probiotic strains were selected for encapsulation (Lactobacillus plantarum CECT 220 and Lactobacillus casei CECT 475) in order to evaluate the ability of SPC to encapsulate and protect bacteria from stress conditions. The viability of these encapsulated strains under in vitro gastrointestinal conditions and shelf-life during storage were compared with the most common forms commercialized nowadays. Results show that SPC is a feasible material for the development of probiotic microparticles with adequate physicochemical properties and enhanced significantly both probiotic viability and tolerance against simulated gastrointestinal fluids when compared to current available commercial forms.

A numerical wave-optical approach for the simulation of analyzer-based x-ray imaging.

An advanced wave-optical approach for simulating a monochromator-analyzer set-up in Bragg geometry with high accuracy is presented. The polychromaticity of the incident wave on the monochromator is accounted for by using a distribution of incoherent point sources along the surface of the crystal. The resulting diffracted amplitude is modified by the sample and can be well represented by a scalar representation of the optical field where the limitations of the usual 'weak object' approximation are removed. The subsequent diffraction mechanism on the analyzer is described by the convolution of the incoming wave with the Green-Riemann function of the analyzer. The free space propagation up to the detector position is well reproduced by a classical Fresnel-Kirchhoff integral. The preliminary results of this innovative approach show an excellent agreement with experimental data.

Influence of moisture content on the mechanical properties of methyl methacrylate-starch copolymers.

The water vapour sorption-desorption behaviour of graft copolymers (hydroxypropylstarch-methyl methacrylate -HSMMA- and carboxymethylstarch-methyl methacrylate -CSMMA-) synthetised by free-radical polymerisation and alternatively dried by oven (OD) or freeze-drying (FD) techniques was investigated in a previous paper. The aim of the present study was to analyse the influence of the amount and distribution of water molecules on the flow and compaction characteristics of this family of methyl methacrylate-starch copolymers. Products were stored at constant temperature (25 degrees C) and different relative humidity conditions (RH). Flow properties of the powdered materials were evaluated using glass and stainless-steel funnels and the densification behaviour was studied in detail by means of Heckel treatment and compression parameters. Results revealed that the storage at 25-50% RH was the optimum condition relating flowability for HSMMA and OD-CSMMA copolymers. At higher RH values, the flow characteristics worsened, due to an increment in cohesive forces. Compaction experiments showed that the 25-50% RH range improved also the compression performance of the copolymers, due to increasing powder compressibility and reduced compact relaxation. Under these circumstances, absorbed water might act as plasticiser and adsorbed water as lubricant.

[Adverse reactions induced by gadopentetate dimeglumine in magnetic resonance imaging]. / Efectos adversos inducidos por gadopentotato dimeglumina en resonancia magnética.

BACKGROUND AND OBJECTIVES: It is considered that the Gadolinium salts used as a contrast medium in the Magnetic Resonance Imaging (MRI) studies present an index of adverse reactions below the iodine contrast mediums. The main objective of this study is to determine, in our medium, the frequency and intensity of the adverse reactions related to the administration of Gadopentotate Dimeglumine (Gd-DTPA) and compare it with the rate of adverse reactions induced by the iodine contrast mediums. MATERIAL AND METHODS: During the period comprised between 1st of January 2005 and 30th of June 2006, the adverse affects were collected for all the studies by means of MRI in which the Gd-DTPA contrast was applied, programmed or urgent, performed in Eresa Diagnosis Centres by Image located ( 11 centre in total) in the provinces of Castellón and Valencia. The adverse effects induced by the iodine salts were also collected in this period. RESULTS: A total of 54,909 studies with magnetic resonance were performed in the referred study centres, and 12,791 studies with MCI. The total of adverse reactions observed was 62 (0.11%) and 47 (0.36%) respectively. The profile of adverse reactions with both contrast mediums was similar, except in the moderate reactions where we objectively observed a greater percentage of palpebral edema and dyspnea with the usage of MCI than with Gd-DTPA. No cases of anaphylaxia or exitus were observed. CONCLUSIONS: The data contributed by this series support a safety profile of Gadolinium superior to that of the MCI in line with the results shown by extensive published series.

Dynamical focusing by bent, asymmetrically cut perfect crystals in Laue geometry.

A semi-analytical approach based on the influence functions of a point source located on the crystal surface has been adopted to show that the focusing ability of cylindrically bent Laue crystals may be strongly enhanced by replacing symmetrically cut crystals with asymmetrically cut crystals. This approach is generally applicable to any distance between the X-ray source and the focusing bent crystal. A mathematically straightforward method to simplify the derivation of the already known expression of the influence functions in the case of deformed crystals with a constant strain gradient (e.g. cylindrically bent crystals) is also presented.