Scale for contraversive pushing in stroke patients: pusher behavior vs Thalamic astasia differential diagnosis and psychometric properties.

BACKGROUND: : Few studies have investigated the psychometric properties of the Scale for Contraversive Pushing (SCP) in depth, and none have evaluated its ability to establish differential diagnosis between pusher behavior (PB) and thalamic astasia (TA). OBJECTIVES: : To study the ability of the SCP to establish differential diagnosis, its reliability, content, construct, and internal validity in the assessment of subacute stroke patients. METHODS: : 120 individuals were evaluated using the SCP over a four-week period of treatment. Intra- and inter-observer reliability, floor and ceiling effects, minimum detectable change (MDC), internal validity and sensitivity to change were explored. In addition, the Barthel Index and the Trunk Control Test were used to study their correlations with the SCP. RESULTS: : Discriminant validity provides evidence that the correlation between SCP items was large or moderate. Convergent validity demonstrated that the correlation of each item with the total score of the scale was high (at around 0.8). Sensitivity to change was large (W = 0.274). Intra- and inter-observer reliability were excellent (Intraclass Correlation Coefficient > 0.9; k > 0.8), except for items B standing and C sitting (k > 0.7). The MDC was 1.39, and ceiling (8.333%) and floor (15.833%) effects were adequate. Cronbach's alpha (α) was equal to 0.901 (0.874-0.924) and McDonald's Omega (ω) was equal to 0.883 (0.856-0.973), showing excellent internal consistency. CONCLUSIONS: : The SCP is a reliable and valid tool which can successfully establish differential diagnosis between PB and TA and evaluate the changes generated by physiotherapy treatment.

Impact of mixing layer height variations on air pollutant concentrations and health in a European urban area: Madrid (Spain), a case study.

The occurrence of local high-pollution episodes in densely populated urban areas, which have huge fleets of vehicles, is currently one of the most worrying problems associated with air pollution worldwide. Such episodes are produced under specific meteorological conditions, which favour the sudden increase of levels of air pollutants. This study has investigated the influence of the mixing layer height (MLH) on the concentration levels of atmospheric pollutants and daily mortality in Madrid, Spain, during the period 2011-2014. It may help to understand the causes and impact of local high-pollution episodes. MLH at midday over Madrid was daily estimated from meteorological radio soundings. Then, days with different MLH over this urban area were characterized by meteorological parameters registered at different levels of an instrumented tower and by composite sea level pressure maps, representing the associated synoptic meteorological scenarios. Next, statistically significant associations between MLH and levels of PM10, PM2.5, NO, NO2, CO and ultra-fine particles number concentrations registered at representative monitoring stations were evaluated. Finally, associations between all-natural cause daily mortality in Madrid, MLH, and air pollutants were estimated using conditional Poisson regression models. The reduction of MLH to values below 482 m above-ground level under strong atmospheric stagnation conditions was accompanied by a statistically significant increase in levels of NO, NO2, CO, PM2.5 and ultra-fine particle number concentrations at urban-traffic and suburban monitoring sites. The decrease of the MLH was also associated to a linear increase of the daily number of exceedances of the UE NO2 hourly limit value (200 µg/m3) and levels of air pollutants at hotspot urban-traffic monitoring stations. Also, a statistically significant association of the MLH with all-natural cause daily mortality was obtained. When the MLH increased by 830 m, the risk of mortality decreased by 2.5% the same day and by 3.3% the next day, when African dust episodic days were excluded. They were also higher in absolute terms than the increases in risk of mortality that were determined for the exposition to any other air pollutant. Our results suggest that when the prediction models foresee values of MLH below 482 m above-ground level in Madrid, the evolution of high-contamination episodes will be very favourable. Therefore, short-term policy measures will have to be implemented to reduce NO, NO2, CO, PM2.5 and ultra-fine particle emissions from anthropogenic sources in this southern European urban location.

Biomass Pyrolysis Solids as Reducing Agents: Comparison with Commercial Reducing Agents.

Biomass is one of the most suitable options to be used as renewable energy source due to its extensive availability and its contribution to reduce greenhouse gas emissions. Pyrolysis of lignocellulosic biomass under appropriate conditions (slow heating rate and high temperatures) can produce a quality solid product, which could be applicable to several metallurgical processes as reducing agent (biocoke or bioreducer). Two woody biomass samples (olives and eucalyptus) were pyrolyzed to produce biocoke. These biocokes were characterized by means of proximate and ultimate analysis, real density, specific surface area, and porosity and were compared with three commercial reducing agents. Finally, reactivity tests were performed both with the biocokes and with the commercial reducing agents. Bioreducers have lower ash and sulfur contents than commercial reducers, higher surface area and porosity, and consequently, much higher reactivity. Bioreducers are not appropriate to be used as top burden in blast furnaces, but they can be used as fuel and reducing agent either tuyére injected at the lower part of the blast furnace or in non-ferrous metallurgical processes where no mechanical strength is needed as, for example, in rotary kilns.

Stellatolides, a new cyclodepsipeptide family from the sponge Ecionemia acervus: isolation, solid-phase total synthesis, and full structural assignment of stellatolide A.

The marine environment is a rich source of metabolites with potential therapeutic properties and applications for humans. Here we describe the first isolation, solid-phase total synthesis, and full structural assignment of a new class of cyclodepsipeptides from the Madagascan sponge Ecionemia acervus that shows in vitro cytotoxic activities at submicromolar concentrations. Seven structures belonging to a new family of compounds, given the general name stellatolides, were characterized. The sequence and stereochemistry of all the amino acids in these molecules were established by a combination of spectroscopic analysis, chemical degradation, and derivatization studies. Furthermore, the complete structure of stellatolide A was confirmed by an efficient solid-phase method for the first total synthesis and the full structural assignment of this molecule, including the asymmetric synthesis of the unique ß-hydroxy acid moiety (Z)-3-hydroxy-6,8-dimethylnon-4-enoic acid.

New serotonin 5-HT1A receptor agonists endowed with antinociceptive activity in vivo.

We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR. Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-{[2-(2-ethoxyphenoxy)ethyl]amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione] has been characterized as a high-affinity and potent 5-HT1AR agonist (Ki = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t1/2 ∼ 3 h and CLint = 3.5 mL/min/kg, at 5 µM), and a low level of protein binding (25%, at 5 µM). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.

New serotonin 5-HT(1A) receptor agonists with neuroprotective effect against ischemic cell damage.

We report the synthesis of new compounds 4-35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT(1A) receptor (5-HT(1A)R). Computational ß(2)-based homology models of the ligand-receptor complexes were used to explain the observed structure-affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT(1A)R agonist (K(i) = 5.9 nM, EC(50) = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.

DABCO-bis(sulfur dioxide), DABSO, as a convenient source of sulfur dioxide for organic synthesis: utility in sulfonamide and sulfamide preparation.

The charge-transfer complex generated from the combination of DABCO and sulfur dioxide, DABSO, is a bench-stable colorless solid suitable for use in organic synthesis as a replacement for gaseous sulfur dioxide. The complex can be combined with Grignard reagents to form sulfinates, which can then be converted in situ to a series of sulfonamides. Alternatively, reaction with anilines and iodine leads to the formation of a series of sulfamides. Cheletropic addition between DABSO and 2,3-dimethylbutadiene provides the corresponding sulfolene.

Benzimidazole derivatives. Part 5: design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands.

A series of new mixed benzimidazole-arylpiperazine derivatives were designed by incorporating in general structure III the pharmacophoric elements of 5-HT(1A) and 5-HT(3) receptors. Compounds 1-11 were synthesized and evaluated for binding affinity at both serotoninergic receptors, all of them exhibiting high 5-HT(3)R affinity (K(i)=10-62nM), and derivatives with an o-alkoxy group in the arylpiperazine ring showing nanomolar affinity for the 5-HT(1A)R (K(i)=18-150nM). Additionally, all the synthesized compounds were selective over alpha(1)-adrenergic and dopamine D(2) receptors (K(i)>1000-10,000nM). Compound 3 was selected for further pharmacological characterization due to its interesting binding profile as mixed 5-HT(1A)/5-HT(3) ligand with high affinity for both receptors (5-HT(1A): K(i)=18.0nM, 5-HT(3): K(i)=27.2nM). In vitro and in vivo findings suggest that this compound acts as a partial agonist at 5-HT(1A)Rs and as a 5-HT(3)R antagonist. This novel mixed 5-HT(1A)/5-HT(3) ligand was also effective in preventing the cognitive deficits induced by muscarinic receptor blockade in a passive avoidance learning test, suggesting a potential interest in the treatment of cognitive dysfunction.

Design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands.

A series of new benzimidazole-arylpiperazine derivatives III were designed, synthesized and evaluated for binding affinity at serotoninergic 5-HT(1A) and 5-HT(3) receptors. Compound IIIc was identified as a novel mixed 5-HT(1A)/5-HT(3) ligand with high affinity for both serotonin receptors and excellent selectivity over alpha(1)-adrenergic and dopamine D(2) receptors. This compound was characterized as a partial agonist at 5-HT(1A)Rs and a 5-HT(3)R antagonist, and was effective in preventing the cognitive deficits induced by muscarinic receptor blockade in a passive avoidance learning test.