"Roberto Rodríguez" General Teaching Hospital of Moron, Ciego De Avila, Cuba, Neurosurgery and Pediatric Intensive Care Services Pediatric Neuromonitoring in Severe Head Trauma.

Among all types of trauma in children, traumatic brain injury has the greatest potential for the development of devastating consequences, with nearly three million affected each year in the world. A controlled, nonrandomized experimental study was carried out in pediatric patients with severe traumatic brain injury, whose objective was to evaluate the use of continuous multimodal neuromonitoring (MMN) of intracranial parameters as a guide in the treatment of children of different age-groups. The patients were divided into two groups according to the treatment received; clinical and imaging monitoring was performed in both.

Synthesis, resolution, and absolute configuration determination of a vicinal amino alcohol with axial chirality. Application to the synthesis of new box and pybox ligands.

New racemic vicinal amino alcohol derivatives with 4-benzylidenecyclohexane skeleton and axial chirality have been prepared. A preparatively easy and efficient protocol for resolution of the N-benzoylamino alcohol is described. Using a 250 × 20 mm (L × ID) Chiralpak® IA column, and the appropriate mixture of n-hexane/ethanol/chloroform as eluent, both enantiomers of N-benzoylamino alcohol 3 are obtained with >99% enantiomeric excess (ee) by successive injections of a solution of the racemic sample in chloroform.

Alchemical Design of Pharmacological Chaperones with Higher Affinity for Phenylalanine Hydroxylase.

Phenylketonuria (PKU) is a rare metabolic disease caused by variations in a human gene, PAH, encoding phenylalanine hydroxylase (PAH), and the enzyme converting the essential amino acid phenylalanine into tyrosine. Many PKU-causing variations compromise the conformational stability of the encoded enzyme, decreasing or abolishing its catalytic activity, and leading to an elevated concentration of phenylalanine in the blood, which is neurotoxic. Several therapeutic approaches have been developed to treat the more severe manifestations of the disorder, but they are either not entirely effective or difficult to adhere to throughout life.

Selective Targeting of Human and Animal Pathogens of the Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies.

Antimicrobial resistant (AMR) bacteria constitute a global health concern. is a Gram-negative bacterium that infects about half of the human population and is a major cause of peptic ulcer disease and gastric cancer. Increasing resistance to triple and quadruple eradication therapies poses great challenges and urges the development of novel, ideally narrow spectrum, antimicrobials targeting .

Debenzylative Cycloetherification as a Synthetic Tool in the Diastereoselective Synthesis of 3,6-Disubstituted Hexahydro-2-furo[3,2-]pyrroles, PDE1 Enzyme Inhibitors with an Antiproliferative Effect on Melanoma Cells.

Two series of novel chiral hexahydro-2-furo[3,2-]pyrroles, 4-(7,8-dimethoxyquinazolin-4-yl) series A and 4-(6,7- dimethoxyquinazolin-4-yl) series B, were synthesized in enantiomerically pure form and evaluated for their inhibitory effects on phosphodiesterase 1 (PDE1) and phosphodiesterase 4 (PDE4) as well as for their inhibitory activity on cell proliferation in A375 melanoma and 3T3 fibroblast cells in vitro. Key steps of synthesis were (i) diastereoselective nucleophilic addition of vinylmagnesium bromide to -allylimine derived from conveniently protected d-glyceraldehyde, (ii) ring-closing metathesis, (iii) debenzylative cycloetherification, and (iv) aromatic nucleophilic substitution. Some of the obtained compounds were proven to be active as inhibitors of PDE1 isoforms, with IC values in the high nanomolar/low micromolar concentration range, and showed antiproliferative activity on A375 melanoma cells.

Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position.

GSK3082 - a hepatitis C virus RNA polymerase inhibitor - and a series of analogues with structural diversity at the 5-position were prepared from a 2,2,4,5-tetrasubstituted pyrrolidine obtained with a well-defined stereochemistry from the 1,3-dipolar cycloaddition of the chiral imino ester derived from leucine tert-butyl ester and (R)-2,3-O-isopropylideneglyceraldehyde with methyl acrylate. The chiral 2,2-dimethyl-1,3-dioxolane moiety provided by the glyceraldehyde served as a synthetic equivalent for different substituents and functional groups and these transformations usually required mild reaction conditions and simple work-up procedures. The inhibitory activity of the resulting GSK3082 analogues was studied in vitro in a cell-based assay of the subgenomic HCV RNA replication system.

A pyrene-inhibitor fluorescent probe with large Stokes shift for the staining of Aβ, α-synuclein, and amylin amyloid fibrils as well as amyloid-containing Staphylococcus aureus biofilms.

Amyloid fibrils formed by a variety of peptides are biological markers of different human diseases, such as Alzheimer's disease, Parkinson's disease, and type II diabetes, and are structural constituents of bacterial biofilms. Novel fluorescent probes offering improved sensitivity or specificity toward that diversity of amyloid fibrils or providing alternative spectral windows are needed to improve the detection or the identification of amyloid structures. One potential source for such new probes is offered by molecules known to interact with fibrils, such as the inhibitors of amyloid aggregation found in drug discovery projects.

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins.

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.

Diastereoselective Construction of the 6-Oxa-2-azabicyclo[3.2.1]octane Scaffold from Chiral α-Hydroxyaldehyde Derivatives by the Aza-Prins Reaction.

(R)-2,3-Di-O-benzylglyceraldehyde and N-tosyl homoallylamine undergo aza-Prins cyclization to afford (1R,5S,7S)-7-[(benzyloxy)methyl]-2-tosyl-6-oxa-2-azabicyclo[3.2.1]octane in a highly diastereoselective manner through an unexpected intramolecular nucleophilic attack.

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins.

New pyrrolidine-based organocatalysts with a bulky substituent at C2 were synthesized from chiral imines derived from ()-glyceraldehyde acetonide by diastereoselective allylation followed by a sequential hydrozirconation/iodination reaction. The new compounds were found to be effective organocatalysts for the Michael addition of aldehydes to nitroolefins and enantioselectivities up to 85% ee were achieved.

Microalgae cultivation in urban wastewater: Coelastrum cf. pseudomicroporum as a novel carotenoid source and a potential microalgae harvesting tool.

The aim of this work was to study the optimal growth and high value-added production of the microalgae Coelastrum cf. pseudomicroporum Korshikov cultivated in urban wastewater. It was observed that C.

Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed.

Opening of intermediate-conductance calcium-activated potassium channels (KC a 3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KC a 3.

Plastic accumulation in the Mediterranean sea.

Concentrations of floating plastic were measured throughout the Mediterranean Sea to assess whether this basin can be regarded as a great accumulation region of plastic debris. We found that the average density of plastic (1 item per 4 m2), as well as its frequency of occurrence (100% of the sites sampled), are comparable to the accumulation zones described for the five subtropical ocean gyres. Plastic debris in the Mediterranean surface waters was dominated by millimeter-sized fragments, but showed a higher proportion of large plastic objects than that present in oceanic gyres, reflecting the closer connection with pollution sources.

High-performance liquid chromatographic enantioseparation of unusual amino acid derivatives with axial chirality on polysaccharide-based chiral stationary phases.

The successful enantioseparation of axially chiral amino acid derivatives containing a cyclohexylidene moiety on an analytical and semipreparative scale was achieved for the first time by HPLC using polysaccharide-based chiral stationary phases. Racemic methyl N-benzoylamino esters, easily obtained by methanolysis of the corresponding 5(4H)-oxazolones, were subjected to chiral HPLC resolution using chiral stationary phases based on immobilized 3,5-dimethylphenylcarbamate derivatives of amylose (Chiralpak(®) IA column) or cellulose (Chiralpak(®) IB column). The behaviour of both selectors under different elution conditions was evaluated and compared.

A novel pan-negative-gating modulator of KCa2/3 channels, fluoro-di-benzoate, RA-2, inhibits endothelium-derived hyperpolarization-type relaxation in coronary artery and produces bradycardia in vivo.

Small/intermediate conductance KCa channels (KCa2/3) are Ca(2+)/calmodulin regulated K(+) channels that produce membrane hyperpolarization and shape neurologic, epithelial, cardiovascular, and immunologic functions. Moreover, they emerged as therapeutic targets to treat cardiovascular disease, chronic inflammation, and some cancers. Here, we aimed to generate a new pharmacophore for negative-gating modulation of KCa2/3 channels.

Chiral iminoesters derived from D-glyceraldehyde in [3 + 2] cycloaddition reactions. Asymmetric synthesis of a key intermediate in the synthesis of neuramidinase inhibitors.

Silver-catalyzed endo-selective and copper-catalyzed exo-selective asymmetric [3 + 2] cycloadditions of acrylates to chiral iminoesters derived from D-glyceraldehyde have been investigated. The reaction diastereoselectively provides highly functionalized pyrrolidines. This approach was used to develop the first asymmetric synthesis of a key intermediate in the synthesis of pyrrolidine influenza neuramidinase inhibitors.

Potential effects of climate change on the water level, flora and macro-fauna of a large neotropical wetland.

Possible consequences of climate change in one of the world's largest wetlands (Ibera, Argentina) were analysed using a multi-scale approach. Climate projections coupled to hydrological models were used to analyse variability in wetland water level throughout the current century. Two potential scenarios of greenhouse gas emissions were explored, both resulting in an increase in the inter-annual fluctuations of the water level.

Stereoselective synthesis and biological evaluation of D-fagomine, D-3-epi-fagomine and D-3,4-epi-fagomine analogs from D-glyceraldehyde acetonide as a common building block.

The stereoselective synthesis of D-fagomine, D-3-epi-fagomine, and D-3-epi-fagomine analogs starting from readily available D-glyceraldehyde acetonide has been achieved. The synthesis involves diastereoselective anti-vinylation of its homoallylimine, ring-closing metathesis, and stereoselective epoxidation followed by regioselective ring-opening or stereoselective dihydroxylation. The lack of a strong activity as glycosidase inhibitors of these compounds could be advantageous for their therapeutic use as chaperones.

Organocatalyzed enantioselective desymmetrization of diols in the preparation of chiral building blocks.

Desymmetrization of diols is a powerful tool to the synthesis of chiral building blocks. Among the different approaches to perform discrimination between both enantiotopic hydroxyl groups, the organocatalytic approach has gained importance in the last years. A diverse range of organocatalysts has been used to efficiently promote this enantioselective transformation and this Minireview examines the different contributions in this field.

Switch in regioselectivity of epoxide ring-opening by changing the organometallic reagent.

The regio- and stereoselective ring-opening of a 2-(2'-oxiranyl)-1,2,3,6-tetrahydropyridine using organometallic reagents is reported. The choice of the organometallic reagent determines the formation of either 2-[(R)-1-hydroxyalkyl]- or 2-[(S)-2-hydroxy-1-alkyl]-1,2,3,6-tetrahydropyridines. The formation of 2-[(S)-2-hydroxy-1-alkyl]-1,2,3,6-tetrahydropyridines is a rare example of epoxide ring-opening with retention of configuration.

Recent advances in enantioselective organocatalyzed anhydride desymmetrization and its application to the synthesis of valuable enantiopure compounds.

Recent years have witnessed increasing interest in the field of asymmetric organocatalysis. In particular, efforts in this field have been devoted to the use of small organic molecules in asymmetric processes based on enantiotopic face discrimination and, only recently, efforts have also been devoted to asymmetric organocatalytic desymmetrization of prochiral substrates-a process based on enantiotopic group discrimination. This critical review documents the advances in the use of organocatalysis for the enantioselective desymmetrization of achiral and meso anhydrides and its application to the synthesis of valuable compounds as reported until 2010 (134 references).

Trainer variability during step training after spinal cord injury: Implications for robotic gait-training device design.

Robotic devices are being developed to automate repetitive aspects of walking retraining after neurological injuries, in part because they might improve the consistency and quality of training. However, it is unclear how inconsistent manual training actually is or whether stepping quality depends strongly on the trainers' manual skill. The objective of this study was to quantify trainer variability of manual skill during step training using body-weight support on a treadmill and assess factors of trainer skill.