[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (II)].

The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS.

[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (I)].

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)].

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October.

Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts.

Development: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)].

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October.

Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts.

Development: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented.

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM.

5'-nucleotidase, cytosolic II genotype, and clinical outcome in patients with acute myeloid leukemia with intermediate-risk cytogenetics.

Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5'-nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy.

An Enzymatic Platform for Primary Amination of 1-Aryl-2-alkyl Alkynes.

Propargyl amines are versatile synthetic intermediates with numerous applications in the pharmaceutical industry. An attractive strategy for efficient preparation of these compounds is nitrene propargylic C(sp)-H insertion. However, achieving this reaction with good chemo-, regio-, and enantioselective control has proven to be challenging.

An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia.

Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT.

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials.

Rapid Activation of Diazirine Biomaterials with the Blue Light Photocatalyst.

Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking.

Origin and Control of Chemoselectivity in Cytochrome Catalyzed Carbene Transfer into Si-H and N-H bonds.

A cytochrome heme protein was recently engineered to catalyze the formation of carbon-silicon bonds via carbene insertion into Si-H bonds, a reaction that was not previously known to be catalyzed by a protein. High chemoselectivity toward C-Si bond formation over competing C-N bond formation was achieved, although this trait was not screened for during directed evolution. Using computational and experimental tools, we now establish that activity and chemoselectivity are modulated by conformational dynamics of a protein loop that covers the substrate access to the iron-carbene active species.

α-DTC Fullerene Performs Significantly Better than β-DTC as Electron Transporting Material in Perovskite Solar Cells.

In this work, two new C isomers, α and β bis(2-(thiophen-2-yl)ethyl)-C-fullerene mono-adducts (DTC), were synthesized, characterized and used as electron transporting materials (ETMs) in perovskite solar cells (PSCs). Our results show that the α isomer improves both the and FF values of the devices, when compared to the results for the β-isomer and to those for phenyl-C-butyric acid methyl ester (PCBM), used as control. Devices based on α-DTC achieved a power conversion efficiency (PCE) of 15.

How medical transport service professionals perceive risk/protective factors with regard to occupational burnout syndrome: Differences and similarities between an Anglo-American and Franco-German model.

Background: Several studies show that professionals in the two main models of pre-hospital care (Franco-German (FG) and Anglo-American (AA)) are exposed to different psychosocial risk factors, with consequences such as burnout syndrome. Few studies provide information on protective factors, nor are there any results on risk/protective factors from the perspective of professionals and comparing both models (FG and AA).

Objective: From the perspective of medical transport (MT) professionals, we aimed to identify the risk/protective factors that may be involved in occupational burnout syndrome (OBS), comparing Franco-German (FG) and Anglo-American (AA) pre-hospital care models, as well as emergency (EMT) and non-emergency (non-EMT) services.

A nucleus-directed bombesin derivative for targeted delivery of metallodrugs to cancer cells.

We have synthesized a set of bombesin derivatives with the aim of exploring their tumor targeting properties to deliver metal-based chemotherapeutics into cancer cells. Peptide QRLGNQWAVGHLL-NH (BN3) was selected based on its high internalization in gastrin-releasing peptide receptor (GRPR)-overexpressing PC-3 cells. Three metallopeptides were prepared by incorporating the terpyridine Pt(II) complex [PtCl(cptpy)]Cl (1) (cptpy = 4'-(4-carboxyphenyl)-2,2':6,2″-terpyridine) at the N-terminus of BN3 or at the N- or N-amino group of an additional Lys residue (1-BN3, Lys-1-BN3 and 1-Lys-BN3, respectively).

Can We Safely Obtain Formal Oxidation States from Centroids of Localized Orbitals?

The use of centroids of localized orbitals as a method to derive oxidation states (OS) from first-principles is critically analyzed. We explore the performance of the closest-atom distance criterion to assign electrons for a number of challenging systems, including high-valent transition metal compounds, π-adducts, and transition metal (TM) carbenes. Here, we also introduce a mixed approach that combines the position of the centroids with Bader's atomic basins as an alternative criterion for electron assignment.

Hydrogen sulfide impacts on inflammation-induced adipocyte dysfunction.

A dual role of hydrogen sulfide (HS) in inflammation is well-reported and recent studies demonstrated adipogenic effects of HS in 3T3-L1 cells. Here, we aimed to investigate the effects of HS on adipocyte differentiation and inflammation. HS concentration in 3T3-L1 culture media was increased during adipocyte differentiation in parallel to adipogenic and Cth gene expression, and its inhibition using DL-Propargyl Glycine (PPG) impaired 3T3-L1 differentiation.

Increased training compensates for OX1R blockage-impairment of spatial memory and c-Fos expression in different cortical and subcortical areas.

It has been suggested that the orexin system modulates learning and memory-related processes. However, the possible influence that training could have on the effect of the blockade of orexin-A selective receptor (OX1R) on a spatial memory task has not been explored. Therefore, the present study attempts to compare the effects of OX1R antagonist SB-334867 infusion on spatial memory in two different conditions in the Morris Water Maze (MWM).

(-)-Epigallocatechin-3-Gallate Antihyperalgesic Effect Associates With Reduced CX3CL1 Chemokine Expression in Spinal Cord.

(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the neuropathic pain alleviation in animal models. Because chemokine fractalkine (CX3CL1) has been suggested as an important signal during neuropathic pain development, this study aimed to investigate whether CX3CL1 expression may be modulated by EGCG treatment reducing hyperalgesia in chronic constriction injured mice. To this end, Balb/c mice were subjected to a chronic constriction injury of sciatic nerve (CCI) and treated with EGCG or vehicle once a day during the first week following surgery.

Occurrence of drugs of abuse in surface water from four Spanish river basins: Spatial and temporal variations and environmental risk assessment.

The present work investigates the occurrence of 22 drugs of abuse (DAs) and metabolites in surface water from four Spanish River basins: Llobregat, Ebro, Jucar and Guadalquivir. To this end, samples were collected from 77 selected sites in two sampling campaigns conducted in 2010 and 2011. Analyses were performed by means of on-line solid phase extraction-liquid chromatography-electrospray-tandem mass spectrometry (on-line SPE-LC-ESI-MS/MS).

Moving from Classical Ru-NHC to Neutral or Charged Rh-NHC Based Catalysts in Olefin Metathesis.

Considering the versatility of oxidation states of rhodium together with the successful background of ruthenium-N-heterocyclic carbene based catalysts in olefin metathesis, it is envisaged the exchange of the ruthenium of the latter catalysts by rhodium, bearing an open-shell neutral rhodium center, or a +1 charged one. In the framework of in silico experiments, density functional theory (DFT) calculations have been used to plot the first catalytic cycle that as a first step includes the release of the phosphine. DFT is, in this case, the tool that allows the discovery of the less endergonic reaction profile from the precatalytic species for the neutral catalyst with respect to the corresponding ruthenium one; increasing the endergonic character when dealing with the charged system.

A Photoactivatable Platinum(IV) Anticancer Complex Conjugated to the RNA Ligand Guanidinoneomycin.

A photoactivatable platinum(IV) complex, trans,trans,trans-[Pt(N3 )2 (OH)(succ)(py)2 ] (succ=succinylate, py=pyridine), has been conjugated to guanidinoneomycin to study the effect of this guanidinum-rich compound on the photoactivation, intracellular accumulation and phototoxicity of the pro-drug. Surprisingly, trifluoroacetic acid treatment causes the replacement of an azido ligand and the axial hydroxide ligand by trifluoroacetate, as shown by NMR spectroscopy, MS and X-ray crystallography. Photoactivation of the platinum-guanidinoneomycin conjugate in the presence of 5'-guanosine monophosphate (5'-GMP) led to the formation of trans-[Pt(N3 )(py)2 (5'-GMP)](+) , as does the parent platinum(IV) complex.

Complementary Binding in Urea-Based Self-Folding Cavitands.

A new family of cavitands bearing urea groups has been prepared. The hosts display a fluxional behavior akin to that of amide analogues. The ureido functions serve a dual role, stabilizing the folded conformer of the receptor and providing stabilization to guests present in the cavity.

Occurrence and Comparative Toxicity of Haloacetaldehyde Disinfection Byproducts in Drinking Water.

The introduction of drinking water disinfection greatly reduced waterborne diseases. However, the reaction between disinfectants and natural organic matter in the source water leads to an unintended consequence, the formation of drinking water disinfection byproducts (DBPs). The haloacetaldehydes (HALs) are the third largest group by weight of identified DBPs in drinking water.