Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

A step towards rational design of carbon nanobelts with tunable electronic properties.

Belt-shaped aromatic compounds are among the most attractive classes of radial π-conjugated nanocarbon molecules with unique physical and chemical properties. In this work, we computationally studied a number of all-carbon and heteroatom-bridged nanobelts, as well as their inclusion complexes with fullerene C60. Our results provide a useful guide for modulating the electronic properties of the nanobelts. An in-depth analysis of the ground and excited state properties of their complexes has allowed us to establish structure-property relationships and propose simple principles for the design of nanobelts with improved electron-donating properties suitable for photovoltaic applications.

Widening the landscape of transcriptional regulation of green algal photoprotection.

Availability of light and CO2, substrates of microalgae photosynthesis, is frequently far from optimal. Microalgae activate photoprotection under strong light, to prevent oxidative damage, and the CO2 Concentrating Mechanism (CCM) under low CO2, to raise intracellular CO2 levels. The two processes are interconnected; yet, the underlying transcriptional regulators remain largely unknown. Employing a large transcriptomic data compendium of Chlamydomonas reinhardtii's responses to different light and carbon supply, we reconstruct a consensus genome-scale gene regulatory network from complementary inference approaches and use it to elucidate transcriptional regulators of photoprotection. We show that the CCM regulator LCR1 also controls photoprotection, and that QER7, a Squamosa Binding Protein, suppresses photoprotection- and CCM-gene expression under the control of the blue light photoreceptor Phototropin. By demonstrating the existence of regulatory hubs that channel light- and CO2-mediated signals into a common response, our study provides an accessible resource to dissect gene expression regulation in this microalga.

Light-independent regulation of algal photoprotection by CO2 availability.

Photosynthetic algae have evolved mechanisms to cope with suboptimal light and CO2 conditions. When light energy exceeds CO2 fixation capacity, Chlamydomonas reinhardtii activates photoprotection, mediated by LHCSR1/3 and PSBS, and the CO2 Concentrating Mechanism (CCM). How light and CO2 signals converge to regulate these processes remains unclear. Here, we show that excess light activates photoprotection- and CCM-related genes by altering intracellular CO2 concentrations and that depletion of CO2 drives these responses, even in total darkness. High CO2 levels, derived from respiration or impaired photosynthetic fixation, repress LHCSR3/CCM genes while stabilizing the LHCSR1 protein. Finally, we show that the CCM regulator CIA5 also regulates photoprotection, controlling LHCSR3 and PSBS transcript accumulation while inhibiting LHCSR1 protein accumulation. This work has allowed us to dissect the effect of CO2 and light on CCM and photoprotection, demonstrating that light often indirectly affects these processes by impacting intracellular CO2 levels.

Aromaticity controls the excited-state properties of host-guest complexes of nanohoops.

π-Conjugated organic molecules have exciting applications as materials for batteries, solar cells, light-emitting diodes, etc. Among these systems, antiaromatic compounds are of particular interest because of their smaller HOMO-LUMO energy gap compared to aromatic compounds. A small HOMO-LUMO gap is expected to facilitate charge transfer in the systems. Here we report the ground and excited-state properties of two model nanohoops that are nitrogen-doped analogs of recently synthesized [4]cyclodibenzopentalenes - tetramers of benzene-fused aromatic 1,4-dihydropyrrolo[3,2-b]pyrrole ([4]DHPP) and antiaromatic pyrrolo[3,2-b]pyrrole ([4]PP). Their complexes with C60 fullerene show different behavior upon photoexcitation, depending on the degree of aromaticity. [4]DHPP acts as an electron donor, whereas [4]PP is a stronger electron acceptor than C60. The ultrafast charge separation combined with the slow charge recombination that we found for [4]PP⊃C60 indicates a long lifetime of the charge transfer state.

Advancements in Dentistry with Artificial Intelligence: Current Clinical Applications and Future Perspectives.

Artificial intelligence has been widely used in the field of dentistry in recent years. The present study highlights current advances and limitations in integrating artificial intelligence, machine learning, and deep learning in subfields of dentistry including periodontology, endodontics, orthodontics, restorative dentistry, and oral pathology. This article aims to provide a systematic review of current clinical applications of artificial intelligence within different fields of dentistry. The preferred reporting items for systematic reviews (PRISMA) statement was used as a formal guideline for data collection. Data was obtained from research studies for 2009-2022. The analysis included a total of 55 papers from Google Scholar, IEEE, PubMed, and Scopus databases. Results show that artificial intelligence has the potential to improve dental care, disease diagnosis and prognosis, treatment planning, and risk assessment. Finally, this study highlights the limitations of the analyzed studies and provides future directions to improve dental care.

Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella.

Plastic degradation by biological systems with re-utilization of the by-products could be a future solution to the global threat of plastic waste accumulation. Here, we report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours' exposure at room temperature under physiological conditions (neutral pH). The wax worm saliva can overcome the bottleneck step in PE biodegradation, namely the initial oxidation step. Within the saliva, we identify two enzymes, belonging to the phenol oxidase family, that can reproduce the same effect. To the best of our knowledge, these enzymes are the first animal enzymes with this capability, opening the way to potential solutions for plastic waste management through bio-recycling/up-cycling.

Nitrogen-doped molecular bowls as electron donors in photoinduced electron transfer reactions.

In recent years, the chemistry of curved π-conjugated molecules has experienced a sharp rise. The inclusion of a heteroatom in the carbon network significantly affects its semiconducting properties. In this work, we computationally study the photoinduced electron transfer in a series of C60 fullerene complexes with experimentally established nitrogen-doped molecular bowls. Our results demonstrate that introducing nitrogen into pentagonal rings of the bowl-shaped π-conjugated molecules and extending the π-conjugation can modulate their electron-transfer properties. Among the studied complexes, the hub-NCor⊃C60 complex exhibits the most desirable combination of ultrafast charge separation and slow charge recombination, suggesting its potential use in photovoltaics.

Role of the gut microbiota in the development of various neurological diseases.

INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.

Dissociation between individual differences in self-reported pain intensity and underlying fMRI brain activation.

Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101). Here we show that pain ratings varied widely across individuals and that individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. Furthermore, brain activation related to interindividual differences in pain was not detected, despite clear sensitivity of the Blood Oxygenation Level-Dependent (BOLD) signal to small differences in noxious stimulus intensities within individuals. These findings suggest fMRI may not be a useful objective measure to infer reported pain intensity.

Economic burden of long-term treatment of severe fecal incontinence.

INTRODUCTION: Find out the long-term economic cost associated with the treatment of severe fecal incontinence by SNS versus symptomatic conservative treatment and definitive colostomy. METHODS: Detailed descriptive study of the costs of the healthcare process (interventions, consultations, devices, complementary tests, hospitalization, etc.) of 3 treatment alternatives for fecal incontinence using analytical accounting tools of the Health Service based on clinical activity data. The frequency of use of health resources or the quantity of products dispensed in pharmacies (medication, diapers, ostomy material, etc.) was estimated in each case. Costs derived from adverse situations were included. Patients with severe fecal incontinence, defined by a score greater than 9 on the Wexner severity scale, in whom first-line treatments had failed, were included. Data from a consecutive cohort of 93 patients who underwent an SNS between 2002 and 2016 were used; patients who underwent definitive colostomy (n=2); parastomal hernia (n=3); and colostomy stenosis (n=1). RESULTS: The mean cumulative cost in 10 years per patient in each alternative was: € 10,972.9 symptomatic treatment (62% diapers); € 17,351.57 SNS (95.83% interventions; 81.6% devices); € 25,858.54 definitive colostomy (70.4% ostomy material and accessories). CONCLUSIONS: Management of severe fecal incontinence implies a great burden in economic terms. The colostomy is the alternative that generates the most direct cost, followed by SNS and symptomatic treatment.

Incidents related to critical patient safety during in-hospital transfer.

OBJECTIVE: To analyze the incidents related to patient safety (IRSP) and their risk factors during in-hospital transfer (IHT) of critical patients after the application of a protocol, and to evaluate safety during transfer using quality indicators. DESIGN: A prospective, observational and non-intervention cohort study was carried out. SETTING: A 10-bed multipurpose Intensive Care Unit (ICU) of a second level university hospital. PATIENTS: All IHTs of critical patients in the ICU for diagnostic tests and to the operating room between March 2011 and March 2017 were included in the study. MAIN MEASUREMENTS: Demographic variables, patient severity, transfer priority, moment of the day, reason and type of transfer team. Pre-transport checklist items and IRSP were collected. A biannual analysis was made of quality indicators designed for IHT. RESULTS: A total of 805 transfers were registered, mostly of an urgent nature (53.7%) and for diagnostic tests (77%). In turn, 112 transfers (13.9%) presented some type of IRSP; 54% related to the equipment and 30% related to team and organization. Adverse events occurred in 19 (2.4%) transfers. Risk factors identified in the multivariate analysis were mechanical ventilation and the transport team. The evolution of the indicators related to transport was significantly favorable. CONCLUSIONS: After the application of an IHT protocol, IRSP are low. The main risk factor is invasive mechanical ventilation. The experience of the team performing IHT influences the detection of a greater number of incidents.

[Mild encephalitis/encephalopathy syndrome with reversible splenial lesion associated with intraventricular bleeding secondary to cavernoma. Findings from the magnetic resonance brain scan]. / Síndrome de encefalitis/encefalopatía leve con lesión del esplenio reversible asociado a sangrado intraventricular secundario a cavernoma. Hallazgos en la resonancia magnética cerebral.

TITLE: Síndrome de encefalitis/encefalopatía leve con lesión del esplenio reversible asociado a sangrado intraventricular secundario a cavernoma. Hallazgos en la resonancia magnética cerebral.

Photoinduced electron transfer in non-covalent complexes of C60 and phosphangulene oxide derivatives.

Investigation of photoinduced electron transfer (PET) in a series of experimentally reported complexes of fullerene with phosphangulene oxides shows that the replacement of O atoms in the bridge of phosphangulene with S atoms promotes efficient and ultrafast ET from phosphangulene oxide to fullerene in PGOOSS⊃C60 and PGOSSS⊃C60 complexes. The results obtained can be useful for the development of photovoltaic devices based on phosphangulenes.

The influence of interferon ß-1b on gut microbiota composition in patients with multiple sclerosis.

INTRODUCTION: The association between gut microbiota and animal models of multiple sclerosis has been well established; however, studies in humans are scarce. METHODS: We performed a descriptive, cross-sectional study comparing the relative composition of gut microbiota in 30 patients with multiple sclerosis (15 treated with interferon ß-1b, 15 not receiving this treatment) and 14 healthy controls using next generation sequencing. RESULTS: Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species. More specifically, we found significant differences in the proportion of Firmicutes, Actinobacteria, and Lentisphaerae and 6 bacteria species between controls and untreated patients; however, these differences disappeared when compared with treated patients. Untreated patients showed a significant reduction in the proportion of Prevotella copri compared to controls, while the bacteria was significantly more abundant in patients treated with interferon ß-1b than in untreated patients, with levels resembling those observed in the healthy control group. CONCLUSION: We observed differences in gut microbiota composition between patients with multiple sclerosis and controls, and between patients treated and not treated with interferon ß-1b. In most cases, no differences were observed between treated patients and healthy controls, particularly for P. copri levels. This suggests that the clinical improvements observed in patients with multiple sclerosis receiving interferon ß-1b may result from the effect of the drug on gut microbiota. Longitudinal and functional studies are necessary to establish a causal relationship.

Toxicology and Biodegradability of a Phthalate-Free and Bio-Based Novel Plasticizer.

Phthalate esters, mainly di-ethylhexylphthalate (DEHP), represent a class of chemicals primarily used as plasticizers for polyvinyl chloride in a wide range of domestic and industrial applications. These phthalate esters are low-toxicity environmental contaminants. To address these drawbacks, POLYSORB® ID 37, a blend of diesters obtained from esterification of isosorbide with plant-based fatty acids, was developed. The company can now offer PVC manufacturers a new product which competes with phthalates and other such chemicals. The market for plasticizers is very important, and ROQUETTE intends to provide a more sustainable and safer product. Isosorbide diester is bio-based (made from glucose and vegetable fatty acids). This plasticizer is registered in REACH regulation for high volumes (>1000 T/year). Risk assessment was obtained by conducting a wide range of biodegradability and toxicological protocols, using rodent models, according to established guidelines. Overall, all of the toxicological and biodegradability studies demonstrated that POLYSORB® ID 37 is nontoxic to mammalian life and is readily biodegradable.