Design, Synthesis, and Evaluation of a Novel Conjugate Molecule with Dopaminergic and Neuroprotective Activities for Parkinson's Disease.

The escalating prevalence of Parkinson's disease (PD) underscores the need for innovative therapeutic interventions since current palliative measures, including the standard l-Dopa formulations, face challenges of tolerance and side effects while failing to address the underlying neurodegenerative processes. Here, we introduce , a novel conjugate molecule that aims to combine symptomatic relief with disease-modifying strategies for PD. Crafted through knowledge-guided chemistry, the molecule combines a nonantibiotic doxycycline derivative with dopamine, preserving neuroprotective attributes while maintaining dopaminergic agonism.

Synthesis of -glycosyl amides: conformational analysis and evaluation as inhibitors of β-galactosidase from .

The synthesis of -glycosyl amides typically involves the use of glycosyl amines as direct precursors, resulting in low yields due to hydrolysis and the loss of stereocontrol through anomerization processes. In this study, a sequential synthesis of -glycosyl amides is proposed, employing glycosyl amines as intermediates obtained from glycosyl azides. Derivatives with , , or configurations were synthesized.

Recyclable photoresins for light-mediated additive manufacturing towards Loop 3D printing.

Additive manufacturing (AM) of polymeric materials enables the manufacturing of complex structures for a wide range of applications. Among AM methods vat photopolymerization (VP) is desired owing to improved efficiency, excellent surface finish, and printing resolution at the micron-scale. Nevertheless, the major portion of resins available for VP are based on systems with limited or negligible recyclability.

Synthesis of sugar enones and their use as powerful synthetic precursors of thiodisaccharides.

Monosaccharide derivatives having a double bond conjugated to a carbonyl (sugar enones or enuloses) are relevant synthetic tools. They are also suitable starting materials, or versatile intermediates, for the synthesis of a wide variety of natural or synthetic compounds with a broad spectrum of biological and pharmacological activities. The preparation of enones is mainly focused on the search for more efficient and diastereoselective synthetic methodologies.

Synthesis of thiodisaccharides related to 4-thiolactose. Specific structural modifications increase the inhibitory activity against β-galactosidase.

In the search for new glycosidase inhibitors, a set of benzyl β-D-Gal--(1→4)-3-deoxy-4-thio-α-D-hexopyranosides was synthesized. Diverse configurations were installed at C-2 and C-4 of the glucose residue. The benzyl glycosidic group was kept intact or substituted by an electron-donating or electron-withdrawing group that could also participate in hydrogen bonding.

Assessment of cardiotoxicity and plasma ropivacaine concentrations after serratus intercostal fascial plane block in an experimental model.

Serratus intercostal fascial plane block (SIFPB) has emerged as an alternative to paravertebral block in breast surgery. It involves the administration of high volumes and doses of local anesthetics (LA) that can potentially reach toxic levels. Ropivacaine is widely used in thoraco-fascial blocks; however, there is no information on the plasma concentrations attained after SIPFB and whether they are associated with cardiotoxicity.

Carbohydrate-Derived Polytriazole Nanoparticles Enhance the Anti-Inflammatory Activity of Cilostazol.

Poly(amide-triazole) and poly(ester-triazole) synthesized from d-galactose as a renewable resource were applied for the synthesis of nanoparticles (NPs) by the emulsification/solvent evaporation method. The NPs were characterized as stable, spherical particles, and none of their components, including the stabilizer poly(vinyl alcohol), were cytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficient encapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for the treatment of intermittent claudication, which is associated with undesired side-effects.

Sodium bicarbonate reverts electrophysiologic cardiotoxicity of ropivacaine faster than lipid emulsions in a porcine model.

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous-lipid-emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity.

External validity of teamwork and leadership behavior in academic labs: evidence from samples in Peru and the U.S.

In this investigation, we tested hypotheses concerning how external validity, in relation to leadership and teamwork, was affected as participants moved from organizational to academic settings. Participants consisted of working business students ( = 159) from two countries, Peru and the United States, who adopted leader/teammate roles across settings. Results indicated that (a) transactional leadership and teamwork behavior demonstrated in organizational contexts were predictive of similar behavior in academic contexts, (b) the cultural setting of the study moderates the carry over effect of teamwork and leadership behavior from organizations to laboratories, and (c) for several leadership and teamwork behaviors, role identity and self-awareness incrementally added to the prediction of similar behaviors in academic contexts.

[A socio-anthropological survey to support communication on Covid-19 in West Africa].

The population's adherence to preventive measures is crucial for the success of the fight against the Covid-19 epidemic, whether it is a question of respecting barrier gestures or vaccination. We conducted a socio-anthropological survey in five countries of the Economic Community of West African States (Burkina Faso, Cape Verde, Côte d'Ivoire, Guinea Bissau, and Sierra Leone) on the representations of Covid-19 that may influence this adherence. Our results showed that raising the awareness of barrier gestures was extremely well-received by the population and is perfectly understood, but that a substantial part of the population denies the presence of Covid-19 in their country, that the transmission of SARS-CoV2 by asymptomatic persons is mostly ignored, that the risk factors of severe forms of the disease are insufficiently known and that a majority of the respondents fear contracting Covid-19 when visiting a health center.

Effects of intravenous lipid emulsions on the reversal of pacing-induced ventricular arrhythmias and electrophysiological alterations in an animal model of ropivacaine toxicity.

Introduction: Ropivacaine is considered to have a wider margin of cardiovascular safety. However, several reports of ventricular arrhythmias (VA) due to ropivacaine toxicity have been documented. Intravenous lipid emulsions (ILEs) have recently been used successfully in the treatment of local anesthetic intoxication.

Photooxidation of thiosaccharides mediated by sensitizers in aerobic and environmentally friendly conditions.

A series of β-d-glucopyranosyl derivates have been synthesized and evaluated in photooxidation reactions promoted by visible light and mediated by organic dyes under aerobic conditions. Among the different photocatalysts employed, tetra--acetyl riboflavin afforded chemoselectively the respective sulfoxides, without over-oxidation to sulfones, in good to excellent yields and short reaction times. This new methodology for the preparation of synthetically useful glycosyl sulfoxides constitutes a catalytic, efficient, economical, and environmentally friendly oxidation process not reported so far for carbohydrates.

Revisiting COVID-19 Communication in Western Africa: A Health Literacy-based Approach to Health Communication.

Adherence to protective measures is a major component of COVID-19 epidemic control. COVID-19 health literacy is a major driver of this adherence, and the evaluation of health literacy levels is the basis for designing an effective communication strategy. We conducted a quantitative socio-anthropological study of the knowledge of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and perception of the prevention messages in Burkina Faso, Cabo Verde, Guinea-Bissau, Ivory Coast, and Sierra Leone.

Diaphragm pacing in a pediatric patient with Acquired Central Hypoventilation syndrome.

Introduction: Diaphragmatic pacemaker is a device that reduces or eliminates the need of mechanical ventilation in patients with chronic respiratory failure who keep the phrenic nerve-diaphragm axis intact, as long as they do not present intrinsic lung disease. Although its implantation has been practiced for deca des, its use is not widespread and to date, there is little published literature about it, mostly related to high spinal cord injury and congenital central hypoventilation syndrome.

Objective: To describe an experience of diaphragmatic pacemaker implantation in a pediatric patient with acquired cen tral hypoventilation syndrome.

Intramolecular azide-alkene cycloaddition-elimination reaction in an aldohex-2-enonic acid derivative.

A 6-azido-2-tosylenolate, obtained from D-glucono-1,5-lactone in six steps, underwent an intramolecular cycloaddition-elimination pathway under mild conditions, yielding a chiral, substituted 5,6-dihydro-4H-pyrrolo[1,2-c]-1,2,3-triazole. The conditions were optimized to give exclusive formation of the triazole. The mechanism appears to involve intramolecular ring closure via a 1,3-dipolar azide-alkene cycloaddition to give a 1,2,3-triazoline, followed by elimination of p-toluenesulfonic acid, leading to aromatization.

Comparative Effects of Sodium Bicarbonate and Intravenous Lipid Emulsions on Reversing Bupivacaine-Induced Electrophysiological Toxicity in a Porcine Experimental Model.

Background: Bupivacaine cardiotoxicity mainly manifests as inhibition of the cardiac sodium channel, which slows conduction, particularly at the ventricular level. Experimental studies have demonstrated that intravenous lipid emulsions (ILEs) can reduce the cardiotoxic effects of bupivacaine, but the extent of these effects is controversial. Sodium bicarbonate (B) represents the standard treatment of toxicity related to sodium channel-blocking drugs.

Synthesis of enantiomerically pure enones (2-benzyloxypyran-3-ones) derived from pentoses.

The useful synthons sugar enones (2-benzyloxypyran-3-ones) derived from pentoses have been prepared starting from 2-acetoxyglycals or benzyl pentopyranosides. The glycals were glycosylated with benzyl alcohol in the presence of a Lewis acid (SnCl or InCl) to give enantioenriched enones (ee = 80-90%). Under catalysis with InCl, benzyl 2-enopyranosides gave also the enones (ee = 87%).

Synthesis, characterization and chemical degradation of poly(ester-triazole)s derived from d-galactose.

α-Azide-ω-alkynyl ester monomers were designed and synthesized in order to obtain hydrolytically degradable polymers. The monomers were prepared from d-galactose, as a renewable resource. Environmentally benign azido-alkyne cycloaddition polymerizations were conducted to afford poly(ester-triazole)s, with complete atom economy.

Design and Synthesis of 2-Acetamido-2,3-dideoxythiodisaccharides via Diastereoselective Conjugate Addition to Sugar Enone O-Acetyl Oximes. Galactosidase Inhibition Studies.

The key step in a new synthesis of 2-acetamido-2,3-dideoxy-(1→4)-thiodisaccharides was the conjugate addition of a 1-thiogalactose derivative to E and Z acetyl oximes derived from sugar enones. This reaction was shown to be completely diastereoselective for both the formation of the thioglycosidic linkage and the configuration of acetyl oxime. The thiodisaccharides have been designed as inhibitors of the β-galactosidase from E.

The effect of depressive symptoms on cognition in patients with fibromyalgia.

Background: Fibromyalgia (FM) patients frequently complain of cognitive problems, but it remains unclear whether these cognitive complaints can be attributed to a dysfunction of the central nervous system or if they can be explained by other factors associated with the disease, such as depression, anxiety and sleep dysfunction.

Methods: One hundred and ten patients with FM were compared with thirty-three patients diagnosed with a depressive disorder (DD) and fifty healthy controls (HC). Several measures of attention and executive functions were used to make these comparisons and the patients were also asked to complete questionnaires on depression, anxiety and sleep quality.

Radiological study to evaluate the spreading of two volumes (10 vs. 20ml) of radiological contrast in the block of cutaneous branches of intercostal nerves in medial axillary line (BRILMA) in a porcine experimental model.

Objective: Interfascial blocks of the thoracic wall are being developed as an alternative to central blocks in breast surgery. However, there are few studies that have evaluated the anatomical extension of the local anaesthetic. The objective of this study was to analyse, using fluoroscopy, the spreading of two volumes (10 vs.

Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process.

The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from l-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition.

Synthesis of Enantiomeric Polyhydroxyalkylpyrrolidines from 1,3-Dipolar Cycloadducts. Evaluation as Inhibitors of a β-Galactofuranosidase.

Enantiomeric 2,3,4-tris(hydroxyalkyl)-5-phenylpyrrolidines have been synthesized from the major cycloadducts obtained by the 1,3-dipolar cycloaddition of sugar enones with azomethine ylides derived from natural amino acids. Reduction of the ketone carbonyl group of the cycloadducts, which possess a basic structure of bicyclic 6-(menthyloxy)hexahydropyrano[4,3-c]pyrrol-7(6H)one, afforded a number of pyrrolidine-based bicyclic systems. A sequence of reactions, which involved hydrolysis of the menthyloxy substituent, reduction, N-protection, and degradative oxidation, afforded varied pyrrolidine structures having diverse configurations and patterns of substitution; in particular, polyhydroxylated derivatives have been obtained.

String Theory Origin of Dyonic N=8 Supergravity and Its Chern-Simons Duals.

We clarify the higher-dimensional origin of a class of dyonic gaugings of D=4  N=8 supergravity recently discovered, when the gauge group is chosen to be ISO(7). This dyonically gauged maximal supergravity arises from consistent truncation of massive IIA supergravity on S^6, and its magnetic coupling constant descends directly from the Romans mass. The critical points of the supergravity uplift to new four-dimensional anti-de Sitter space (AdS4) massive type IIA vacua.

Stereospecific synthesis of pyrrolidines with varied configurations via 1,3-dipolar cycloadditions to sugar-derived enones.

Enantiomerically pure pyrrolidines have been obtained by 1,3-dipolar cycloaddition of stabilized azomethine ylides and sugar enones (dihydropyranones) derived from pentoses. Thus, the S-enone (menthyl 3,4-dideoxy-(1S)-pent-3-enopyranosid-2-ulose) was prepared from D-xylose, while the R analogue was obtained from L-arabinose. The dipoles were generated in situ from α-arylimino esters of common amino acids (glycine, alanine, or phenylalanine) and aromatic aldehydes (benzaldehyde, 3-formylpyridine and 4-methoxybenzaldehyde).