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Resumen: Introducción: El síndrome de piernas inquietas (SPI) es un trastorno caracterizado por la necesidad imperiosa de mover las piernas, estando a menudo acompañado de sensaciones desagradables. Su frecuencia es superior en pacientes con esclerosis múltiple (EM) que en la población general. Objetivos: Evaluar la prevalencia del SPI, según el cumplimiento de los 4 requisitos esenciales incluidos en los criterios diagnósticos propuestos por la International Restless leg syndrome study group (IRLSSG, 2003), en una cohorte de pacientes con EM e identificar posibles factores de riesgo y repercusión clínica. Resultados: Se incluyeron 120 pacientes con EM, con una edad media de inicio de 40 años y un tiempo medio de evolución de 46 meses. La prevalencia de SPI, según el cumplimiento de criterios diagnósticos de la IRLSSG, fue del 23,3%. El tiempo de evolución de EM, desde la aparición de los primeros síntomas, fue significativamente menor en pacientes con SPI (p=0,001). La presencia de un brote reciente, así como de síntomas de ansiedad, depresión y dolor neuropático se asociaron de forma significativa con el riesgo de SPI (p=0,001, p

The method describes pigment analysis from microalgae/phytoplankton extracts using electron-transfer Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (ET MALDI MS). Current microalgae/phytoplankton pigment analysis requires resource- and time-intensive chromatographic methods due to the broad polarity range of the target analytes. On the other hand, traditional MALDI MS chlorophyll analysis, using proton-transfer matrices such as 2,5-dihydroxybenzoic acid (DHB) or α-cyano-4-hydroxycinnamic acid (CHCA), results in central metal loss and phytol–ester cleavage. ET MALDI MS is an alternative for the rapid screening and detection of pigments in microalgae extracts. • MALDI matrices with ionization energies above 8.0 eV guarantee electron-transfer processes from photosynthetic and photoprotective pigments whose ionization energies lay below 7.5 eV. • ET MALDI MS pigment analysis agrees with data gathered from conventional chromatographic techniques (HPLC) and optical microscopy for pigment extracts from C. vulgaris cultures and freshwater phytoplankton samples. • The ET MALDI MS method allows fast and reliable detection of pigments in microalgae cultures and freshwater phytoplankton samples.

Aim. To evaluate the effectiveness on tissue response of the new nutritional supplement made of oligomeric proanthocyanidins in induced gingivitis after 21 days of use. Material and Methods. A prospective, double-blind, randomized, controlled clinical trial was carried out on 20 patients; it is divided into an experimental group and a control group after fulfilling the selection criteria. Patients had to come 4 times during the study to register the Silness and Löe index, the gingival bleeding index, the plaque index, the inflammatory crevicular fluid study (IL6), and the changes in the brightness of the gingiva. No complementary hygiene methods were allowed during the 21 days. Results. The Silness and Löe index was higher in the control group than in the experimental group, reaching a twofold difference between the groups (p

Antecedentes: La psoriasis es una enfermedad inflamatoria, sistémica y crónica que afecta a 2.9 % de los mexicanos. La enfermedad se asocia a comorbilidades metabólicas e inflamatorias. Objetivo: Conocer la distribución de los subtipos de psoriasis y determinar las comorbilidades asociadas en un hospital de tercer nivel de la Ciudad de México. Material y métodos: Estudio descriptivo, observacional, retrospectivo y transversal de pacientes con psoriasis (1999- 2023). Se recopiló información sobre edad, sexo, subtipo, año de diagnóstico y defunción, evolución, índice de severidad y comorbilidades. Las variables cualitativas se describieron en frecuencias y porcentajes; las cuantitativas, con media y desviación estándar. Se realizó regresión logística para evaluar asociaciones. Resultados: Se incluyeron 221 pacientes (116 hombres) con edad promedio de 55 años. La psoriasis en placas fue el subtipo más frecuente (85 %) y las comorbilidades principales fueron dislipidemias (33 %) e hipertensión arterial sistémica (33 %). Los hombres presentaron más psoriasis en placas (97 % versus 75 %) y las mujeres, más psoriasis palmoplantar (9.5 % versus 0.9 %). Conclusiones: La asociación con comorbilidades metabólicas y cardiovasculares resalta la necesidad del manejo multidisciplinario y detección temprana. Se destaca la importancia de investigar la psoriasis en México para mejorar la prevención, tratamiento y guiar políticas de salud pública.

Quantum dots (QDs) semiconducting nanomaterials, have garnered attention due to their distinctive properties, including small size, high luminescence, and biocompatibility. In the context of triple-negative breast cancer (TNBC), notorious for its resistance to conventional treatments, QDs exhibit promising potential for enhancing diagnostic imaging and providing targeted therapies. This review underscores recent advancements in the utilization of QDs in imaging techniques, such as fluorescence tomography and magnetic resonance imaging, aiming at the early and precise detection of tumors. Emphasis is placed on the significance of QD design, synthesis and functionalization processes as well as their use in innovative strategies for targeted drug delivery, capitalizing on their ability to selectively deliver therapeutic agents to cancer cells. As the research in this field advances rapidly, this review covers a classification of QDs according to their composition, the characterization techniques than can be used to determine their properties and, subsequently, emphasizes recent findings in the field of TNBC-targeting, highlighting the imperative need to address challenges, like potential toxicity or methodologies standardization. Collectively, the findings explored thus far suggest that QDs could pave the way for early diagnosis and effective therapy of TNBC, representing a significant stride toward precise and personalized strategies in treating TNBC., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Background: The treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles., Objective: The aim of this study was to assess neurologists' preferences for different NMOSD treatment attributes using conjoint analysis (CA)., Methods: We conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs' attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences., Results: A total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts., Conclusion: Neurologists' treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition., Competing Interests: Declaration of competing interest R.G-B, P.L-L, and J.M are employees of Roche Farma Spain. P.R is an employee of IQVIA Spain. N.T-L received compensation for consulting services, advisory activities and speaking honoraria from Bayer Schering Pharma, Biogen Idec, MerckSerono, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche Pharma and Bristol Myers Squibb. M.S received speaking honoraria from Roche, Biogen and UCB Pharma, and travel reimbursement from Biogen, Sanofi, Merck and Roche for national and international meetings. A.O received research grants, travel support or honoraria for speaking engagements from Almirall, Biogen, Bristol Myers Squibb, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. M.D-S received speaking honoraria from Roche, Biogen, Novartis, Sanofi and Janssen; and travel reimbursement from Biogen for international meeting. SB received research grants, travel support or honoraria for speaking engagements from Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. M.A-V received speaking honoraria from Roche, Biogen, Novartis, Sanofi and Janssen. A.CC has received grant from Instituto de Salud Carlos III, Spain; JR19/00,007. A preliminary report of this data was presented as an eposter at the 9th Congress of the European Academy of Neurology (EPV-505, Budapest, Hungary; July 1–4, 2023)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction and Objective: Limited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists' TI in NMOSD., Methods: An online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists' characteristics and TI., Results: A total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0-46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0-11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0-12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient's tolerability/safety when choosing a treatment were predictors of TI., Conclusion: TI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care., Competing Interests: ÁC-C has received a grant from Instituto de Salud Carlos III, Spain; JR19/00007. RG-B, PL-L, and JM are employees of Roche Pharma Spain. PR is an employee of IQVIA, Madrid. NTL received compensation for consulting services, advisory activities and speaking honoraria from Bayer Schering Pharma, Biogen Idec, MerckSerono, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche Pharma, and Bristol Myers Squibb. MS received speaking honoraria from Roche, Biogen, and UCB Pharma, and travel reimbursement from Biogen, Sanofi, Merck, and Roche for national and international meetings. AO received research grants, travel support or honoraria for speaking engagements from Almirall, Biogen, Bristol Myers Squibb, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. MD received speaking honoraria from Roche, Biogen, Novartis, Sanofi, and Janssen; and travel reimbursement from Biogen for international meetings. SB received research grants, travel support or honoraria for speaking engagements from Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. MA-V received speaking honoraria from Roche, Biogen, Novartis, Sanofi, and Janssen., (Copyright © 2024 Cobo-Calvo, Gómez-Ballesteros, Orviz, Díaz Sánchez, Boyero, Aguado-Valcarcel, Sepúlveda, Rebollo, López-Laiz, Maurino and Téllez Lara.)

Introduction: The Andalusian Registry of Pregnancies in patients with multiple sclerosis is the largest Spanish registry on multiple sclerosis (MS) and family planning. For the first time, it includes information on the fertility of men with MS. The influence of the use of a disease-modifying treatment (DMT) on the health of the foetus/newborn and the impact of breastfeeding on MS are also analysed., Subjects and Methods: This is a multicentre, prospective and observational study. Recruitment of patients took place between December 2018 and December 2020. Women were followed up for one year after delivery. Altogether 100 women and 16 men were included, with a total of 103 newborn infants., Results: The annualised relapse rate of the women with MS decreased significantly during pregnancy (from 0.23 to 0.065). A total of 11.2% of patients resorted to assisted reproductive techniques in order to conceive a child. No association was found between the use of a DMT at conception and/or pregnancy and the risk of miscarriage, prematurity or low birth weight. Over half the women with MS (54.2%) chose to breastfeed (26.7% of them while on a DMT)., Conclusions: MS does not affect the fertility of men. Neither does the use of a DMT at the time of conception affect their fertility or their children's health. Assisted reproductive techniques did not have a negative impact on the course of MS. Breastfeeding is a common practice among women with MS and there is no evidence of positive or negative effects on disease progression.

Aims: The fight against cancer is an active research topic that combines several disciplines to find suitable agents to treat various tumours., Background: Following cisplatin, organometallic compounds, including titanocene derivatives, have been tested as antitumoral agents. However, key issues still need to be addressed in metallodrug chemotherapy relating to solubility, stability, and dosage. Mesoporous silica nanoparticles, being low toxic biocompatible materials with high loading capacity, are ideal candidates to overcome these problems., Objective: This study aimed to prepare and structurally characterize titanocene functionalized mesoporous silica nanoparticles and evaluate their cytotoxic activity against cancer cells., Methods: The preparation of titanocene functionalized mesoporous silica nanoparticles was achieved by synthetic protocols, involving either grafting or tethering. Characterization was carried out using standard techniques, FT-IR, XRD, XRF, TEM, and BET. The titanocene functionalized materials were studied as antitumoral agents in the breast cancer lines MCF-7 and MDA-MB-231., Results: The functionalized MSN showed promising antitumoral activity against cells lines MCF-7 and MDAMB- 231 up to 9 times more than titanocene alone., Conclusion: This study reported the potential of titanocene-functionalized mesoporous silica nanoparticles in future chemotherapeutic actions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452 , CD4 rs951818 , and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan -based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452 , CD4 rs951818 , and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452 , CD4 rs951818 , and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population.

Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disease with no cure to date. Therapeutic agents used to treat ALS are very limited, although combined therapies may offer a more effective treatment strategy. Herein, we have studied the potential of nanomedicine to prepare a single platform based on mesoporous silica nanoparticles (MSNs) for the treatment of an ALS animal model with a cocktail of agents such as leptin (neuroprotective) and pioglitazone (anti-inflammatory), which have already demonstrated promising therapeutic ability in other neurodegenerative diseases. Our goal is to study the potential of functionalized mesoporous materials as therapeutic agents against ALS using MSNs as nanocarriers for the proposed drug cocktail leptin/pioglitazone ( MSN-LEP-PIO ). The nanostructured materials have been characterized by different techniques, which confirmed the incorporation of both agents in the nanosystem. Subsequently, the effect, in vivo , of the proposed drug cocktail, MSN-LEP-PIO , was used in the murine model of TDP-43 proteinopathy (TDP-43 A315T mice). Body weight loss was studied, and using the rotarod test, motor performance was assessed, observing a continuous reduction in body weight and motor coordination in TDP-43 A315T mice and wild-type (WT) mice. Nevertheless, the disease progression was slower and showed significant improvements in motor performance, indicating that TDP-43 A315T mice treated with MSN-LEP-PIO seem to have less energy demand in the late stage of the symptoms of ALS. Collectively, these results seem to indicate the efficiency of the systems in vivo and the usefulness of their use in neurodegenerative models, including ALS.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

Introduction: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population., Objectives: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS., Results: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P=.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P=.001, P<.001, P<.001, and P=.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P=.002, P=.017, P=.013, and P=.009, respectively)., Conclusions: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS., (Copyright © 2019 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1-S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

Background: Several variants of the SARS-CoV-2 have been documented globally during the current COVID-19 pandemic. The N501Y, 69-70del, K417N, and E484K SARS-CoV-2 mutations have been documented among the most relevant due to their potential pathogenic biological effects. This study aimed to design, validate, and propose a fast real-time RT-qPCR assay to detect SARS-CoV-2 mutations with possible clinical and epidemiological relevance in the Mexican population., Methods: Targeting spike ( S ) gene mutations of SARS-CoV-2 (N501Y, 69-70del, K417N, and E484K), specific primers, and probes for three specific quantitative reverse transcription PCR (RT-qPCR) assays were designed, and validated using Sanger sequencing. These assays were applied in clinical samples of 1060 COVID-19 patients from Jalisco Mexico., Results: In silico analyzes showed high specificity of the three assays. Amplicons of samples were confirmed through sequencing. The screening of samples of COVID-19 patients allowed the identification of the E484K mutation in nine individuals and the identification of P.2 Brazilian variant in Mexico., Conclusion: This work provides low-cost RT-qPCR assays for rapid screening and molecular surveillance of mutations with potential clinical impact. This strategy allowed the detection of E484K mutation and P.2 variant for the first time in samples from the Mexican population., Competing Interests: Authors RS-S, AV-L, RV-Z, BG-O, MD-S, and OG-G have a working relationship with Genes2Life SAPI de CV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vega-Magaña, Sánchez-Sánchez, Hernández-Bello, Venancio-Landeros, Peña-Rodríguez, Vega-Zepeda, Galindo-Ornelas, Díaz-Sánchez, García-Chagollán, Macedo-Ojeda, García-González and Muñoz-Valle.)

The possible role of oxidative stress and nitric oxide (NO) in the pathogenesis of multiple sclerosis (MS) has been suggested by several neuropathological, biochemical, and experimental data. Because the single-nucleotide polymorphism (SNP) rs2070744 in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) showed association with the risk for MS in Iranians, we attempted to replicate the possible association between this SNP and the risk for MS in the Caucasian Spanish population. The frequencies of NOS3rs2070744 genotypes and allelic variants in 300 patients diagnosed with MS and 380 healthy controls were assessed with a TaqMan-based qPCR assay. The possible influence of the genotype frequency on age at onset of MS, the severity of MS, clinical evolutive subtypes of MS, and HLA-DRB1*1501 genotype were also analyzed. The frequencies of rs2070744 genotypes and allelic variants were not associated with the risk of developing MS and were not influenced by gender, age at onset and severity of MS, the clinical subtype of MS or the HLA-DRB1*1501 genotype. This study found a lack of association between NOS3 rs2070744 SNP and the risk for MS in Caucasian Spanish people.

A series of copper-functionalized SBA-15 (Santa Barbara Amorphous) materials containing the ligands triethoxysilylpropylmaleamic acid (maleamic) or triethoxy-3-(2-imidazolin-1-yl)propylsilane (imidazoline) have been prepared. The nanostructured silica-based systems SBA-maleamic, SBA-imidazoline, SBA-maleamic-Cu and SBA-imidazoline-Cu were characterized by several methods observing that the functionalization took place mainly inside the pores of the mesoporous system. The antimicrobial behaviour of the synthesized materials against Staphylococcus aureus and Escherichia coli was tested observing a very potent activity of the copper-functionalized systems (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for SBA-maleamic-Cu of ca. 31.25 μg/mL, which correspond with ca. 1.13 μg/mL of Cu). A study of the oxidative stress promoted by the synthesized materials showed that the SBA-maleamic-Cu and the SBA-imidazoline-Cu were able to increase the reactive oxygen species (ROS) production in S. aureus by 427% and 373%, respectively, while this increase was slightly lower in E. coli (387 and 324%, respectively). Furthermore, an electrochemical study was carried out in order to determine if these materials interact with lysine or alanine to validate a potential antimicrobial mechanism based on the inhibition of the synthesis of the peptidoglycan of the bacterial wall. Finally, these studies were also performed to determine the potential interaction of the copper-containing materials with glutathione in order to assess if they are able to perturb the metabolism of this tripeptide., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2018. Published by Elsevier Inc.)

Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph 3 Sn{SCH 2 CH 2 CH 2 Si(OMe) 3 } (MSN-AP-Sn), a folate fragment (MSN-AP-FA-Sn), and an enzyme-responsive peptide able to release the metallodrug only inside cancer cells (MSN-AP-FA-PEP-S-Sn), have been synthesized and fully characterized by applying physico-chemical techniques. After that, an in vitro deep determination of the therapeutic potential of the achieved multifunctional nanovectors was carried out. The results showed a high cytotoxic potential of the MSN-AP-FA-PEP-S-Sn material against triple negative breast cancer cell line (MDA-MB-231). Moreover, a dose-dependent metallodrug-related inhibitory effect on the migration mechanism of MDA-MB-231 tumor cells was shown. Subsequently, the organotin-functionalized nanosystems have been further modified with the NIR imaging agent Alexa Fluor 647 to give three different theranostic silica-based nanoplatforms, namely, MSN-AP-Sn-AX (AX-1), MSN-AP-FA-Sn-AX (AX-2), and MSN-AP-FA-PEP-S-Sn-AX (AX-3). Their in vivo potential as theranostic markers was further evaluated in a xenograft mouse model of human breast adenocarcinoma. Owing to the combination of the receptor-mediated site targeting and the specific fine-tuned release mechanism of the organotin metallodrug, the nanotheranostic drug MSN-AP-FA-PEP-S-Sn-AX (AX-3) has shown targeted diagnostic ability in combination with enhanced therapeutic activity by promoting the inhibition of tumor growth with reduced hepatic and renal toxicity upon the repeated administration of the multifunctional nanodrug.

The present systematic review and meta-analysis was carried out to determine the extent to which supracrestal tissue attachment (STA) thickness affects marginal bone loss (MBL) around dental implants. An electronic search was conducted in PubMed (MEDLINE), EMBASE, and complementary sources covering the period up to June 2018. The studies were meta-analyzed based on implant position with respect to the alveolar bone crest (crestal/supracrestal). The MBL values were categorized according to STA width (thick/thin). Of the 1062 eligible titles, nine articles were included in the review. The implants were positioned crestal or supracrestal with respect to the alveolar ridge. The difference between (thin/thick) STA was statistically significant among analytical subsets in terms of lesser MBL (crestal-positioned: weighted mean difference [WMD] = 0.52, 95% CI [0.03-1.01]; P = 0.036; supracrestal-positioned: WMD = 1.26; 95% CI [1.12-1.39]; P = 0.00; pooled analysis: WMD = 0.73; 95% CI [0.033-1.13]; P < 0.01). Implant positioning and patient age showed statistical significance in the meta-regression analysis. The heterogeneity explained by age was R 2  = 39.8%. Despite its limitations, the present study demonstrates that implants with thin STA result in greater MBL. There is moderate certainty of the evidence for a large effect of MBL prevention "in favor" of a thick STA environment in crestal-positioned implants and the pooled analysis, but lesser certainty when only supracrestal-positioned implants are considered. No trials studying this topic in subcrestal-positioned implants were found., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The detection of IgG aquaporin-4 antibodies in the serum of patients with Neuromyelitis optica (NMO) has dramatically improved the diagnosis of this disease and its distinction from multiple sclerosis. Recently, a group of patients have been described who have an NMO spectrum disorder (NMOsd) and who are seronegative for AQP4 antibodies but positive for IgG aquaporin-1 (AQP1) or myelin oligodendrocyte glycoprotein (MOG) antibodies. The purpose of this study was to determine whether AQP1 and MOG could be considered new biomarkers of this disease; and if point mutations in the gDNA of AQP4 , AQP1 and MOG genes could be associated with the etiology of NMOsd. We evaluated the diagnostic capability of ELISA and cell-based assays (CBA), and analyzed their reliability, specificity, and sensitivity in detecting antibodies against these three proteins. The results showed that both assays can recognize these antigen proteins under appropriate conditions, but only anti-AQP4 antibodies, and not AQP1 or MOG, appears to be a clear biomarker for NMOsd. CBA is the best method for detecting these antibodies; and serum levels of AQP4 antibodies do not correlate with the progression of this disease. So far, the sequencing analysis has not revealed a genetic basis for the etiology of NMOsd, but a more extensive analysis is required before definitive conclusions can be drawn.

CD39, an ectonucleotidase that hydrolyses pro-inflammatory ATP, is a marker of highly active and suppressive T regulatory cells (Tregs). Although CD39 has a role in Treg suppression and might be important in the control of neuroinflammation in relapsing-remitting multiple sclerosis (RR-MS), to date, there are contradictory reports concerning the Tregs expression of CD39 in RR-MS patients. Thus, our objectives were to assess the activity and expression of CD39, especially in Tregs from peripheral blood mononuclear cells (PBMCs) of relapsing RR-MS patients compared with control subjects and to evaluate the association of CD39+ Tregs with disability and the odds of RR-MS. The activity and expression of CD39 and the CD39 + Treg frequency were measured in PBMCs from 55 relapsing RR-MS patients (19 untreated and 36 receiving immunomodulatory treatment) and 55 age- and sex-paired controls. Moreover, the association between CD39 + Tregs and RR-MS was assessed by multivariate logistic regression. CD39 activity and the frequency of CD39-expressing Tregs were elevated in relapsing RR-MS patients. Moreover, CD39 + Tregs were significantly correlated with the EDSS score and were independently associated with the odds of RR-MS. Our results highlight the relevance of CD39 + Treg subset in the clinical outcomes of RR-MS.

Objectives: Multiple sclerosis (MS) is the most common chronic disabling disease of the central nervous system (CNS) in young adults. It is characterized by the presence of multiple demyelinating inflammatory lesions disseminated in the CNS. Pseudotumoral lesions (PL) are rarely observed in patients with MS., Methods: These atypical lesions can pose a diagnostic problem, especially when they are present at disease onset., Results: Most MS patients with PLs only have a single episode throughout their disease course, which reflects its low tendency of recurrence., Conclusions: We report the rare case of a 34-year-old MS patient who suffered from recurrent pseudotumoral episodes during follow-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Colorimetric assays based on gold nanoparticles (GNPs) are of considerable interest for diagnostics because of their simplicity and low-cost. Nevertheless, a deep understanding of the interaction between the GNPs and the intended molecular target is critical for the development of reliable detection technologies. The present report describes the spontaneous interaction between HPV16 L1 virus-like particles (VLPs) and non-functionalized GNPs (nfGNPs) resulting in the inhibition of nfGNPs salt-induced aggregation and the stabilization of purified VLPs. Ionic-competition experiments suggested that the nature of nfGNPs-VLPs interaction is non-covalent. Adsorption of an RNA aptamer on nfGNPs surface showed an additive aggregation-inhibitory effect. The use of mutant VLPs confirmed that the interaction nfGNPs-VLPs is not mediated by the opposing superficial electrostatic charges, suggesting that non-electrostatic forces participate in the arrangement of nfGNPs on the VLPs surface. Competition experiments using increasing ethanol concentrations on nfGNPs-VLPs complexes suggested hydrophobic interactions as the main stabilizing force. Therefore, the nfGNPs-VLPs interaction described here should facilitate the development of adsorption assays based on nfGNPs for HPV detection and cervical cancer prevention., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17, and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in patients with MS, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in patients with MS. However, no study has examined melatonin's effect on T cells from relapsing-remitting MS (RR-MS) patients. Therefore, the objectives of the present study were to evaluate the effects of the in vitro administration of melatonin to peripheral blood mononuclear cells (PBMCs) from 64 RR-MS patients and 64 sex- and age-matched healthy subjects on Th1, Th9, Th17, Th22, and Treg responses and to analyze the expression of the melatonin effector/receptor system in these cells. Melatonin decreased Th1 and Th22 responses in patients, whereas it did not affect the Th17 and Treg subsets. Melatonin also promoted skewing toward a more protective cytokine microenvironment, as shown by an increased anti-inflammatory/Th1 ratio. Furthermore, for the first time, we describe the overexpression of the melatonin effector/receptor system in PBMCs from patients with MS; this alteration might be relevant to the disease because acetylserotonin O-methyltransferase expression significantly correlates with disease progression and T effector/regulatory responses in patients. Therefore, our data suggest that melatonin may be an effective treatment for MS., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Detection of IgG anti-Aquaporin-4 (AQP4) in serum of patients with Neuromyelitis optica syndrome disorders (NMOSD) has improved diagnosis of these processes and differentiation from Multiple sclerosis (MS). Recent findings also claim that a subgroup of patients with NMOSD, serum negative for IgG-anti-AQP4, present antibodies anti-AQP1 instead. Explore the presence of IgG-anti-AQP1 using a previously developed cell-based assay (CBA) highly sensitive to IgG-anti-AQP4. Serum of 205 patients diagnosed as NMOSD (8), multiple sclerosis (94), optic neuritis (39), idiopathic myelitis (29), other idiopathic demyelinating disorders of the central nervous system (9), other neurological diseases (18) and healthy controls (8), were used in a CBA over fixed HEK cells transfected with hAQP1-EGFP or hM23-AQP4-EGFP, treated with Triton X-100 and untreated. ELISA was also performed. Analysis of serum with our CBA indicated absence of anti-AQP1 antibodies, whereas in cells pretreated with detergent, noisy signal made reliable detection impossible. ELISA showed positive results in few serums. The low number of NMOSD serums included in our study reduces its power to conclude the specificity of AQP1 antibodies as new biomarkers of NMOSD. Our study does not sustain detection of anti-AQP1 in serum of NMOSD patients but further experiments are expected.

Several neurochemical, neuropathological, and experimental data suggest a possible role of oxidative stress in the ethiopathogenesis of multiple sclerosis(MS). Heme-oxygenases(HMOX) are an important defensive mechanism against oxidative stress, and HMOX1 is overexpressed in the brain and spinal cord of MS patients and in experimental autoimmune encephalomyelitis(EAE). We analyzed whether common polymorphisms affecting the HMOX1 and HMOX2 genes are related with the risk to develop MS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations(CNVs) of these genes in 292 subjects MS and 533 healthy controls, using TaqMan assays. The frequencies of HMOX2 rs1051308AA genotype and HMOX2 rs1051308A and HMOX1 rs2071746A alleles were higher in MS patients than in controls, although only that of the SNP HMOX2 rs1051308 in men remained as significant after correction for multiple comparisons. None of the studied polymorphisms was related to the age at disease onset or with the MS phenotype. The present study suggests a weak association between HMOX2 rs1051308 polymorphism and the risk to develop MS in Spanish Caucasian men and a trend towards association between the HMOX1 rs2071746A and MS risk.

Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10(-/-) compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10(-/-) mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts., (Copyright © 2015 the American Physiological Society.)

Background: Cell-based assays for neuromyelitis optica (NMO) diagnosis are the most sensitive and specific methods to detect anti-aquaporin 4 (AQP4) antibodies in serum, but some improvements in their quantitative and specificity capacities would be desirable. Thus the aim of the present work was to develop a sensitive quantitative method for detection of anti-AQP4 antibodies that allows clear diagnosis of NMO and distinction of false labeling produced by natalizumab treatment., Methods: Sera from 167 individuals, patients diagnosed with NMO (16), multiple sclerosis (85), optic neuritis (24), idiopathic myelitis (21), or other neurological disorders (13) and healthy controls (8), were used as the primary antibody in an immunofluorescence assay on HEK cells transfected with the M23 isoform of human AQP4 fused with enhanced green fluorescent protein. Cells used were freshly transfected or stored frozen and then thawed just before adding the serum., Results: Microscopic observation and fluorescence quantification produced similar results in fresh and frozen samples. Serum samples from patients diagnosed with NMO were 100% positive for anti-AQP4 antibodies, while all the other sera were negative. Using serum from patients treated with natalizumab, a small and unspecific fluorescent signal was produced from all HEK cells, regardless of AQP4 expression., Conclusions: Our cell-based double-label fluorescence immunoassay protocol significantly increases the signal specificity and reduces false diagnosis of NMO patients, especially in those receiving natalizumab treatment. Frozen pretreated cells allow faster detection of anti-AQP4 antibodies.

Background: A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population., Methods: We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays., Results: NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS., Conclusions: Our results indicate that NQO1 rs1800566 does not have an effect on MS disease risk.

Background: The pseudotumoral form of multiple sclerosis (MS) is a rare condition with few descriptions in the literature. It supposes a diagnostic challenge especially when appearing at the onset of disease., Methods: We retrospectively describe a case series of pseudotumoral MS patients that attended our hospital from 2004, analyzing demographic, clinical and radiological variables. We classified the lesions according to the recently proposed morphologic classification (infiltrative, megacystic, Baló or ring-like) and according to the contrast enhancement pattern (nodular, complete ring, incomplete ring and diffuse)., Results: Fourteen patients (11 female, 3 male), with a mean age of 35 years, were identified. All of them suffered from a relapsing-remitting form of MS. Eleven patients (78.57%) had symptomatic pseudotumoral lesions (PL), being the form of clinical presentation in the majority of those patients that were symptomatic (81.81%). Several patients presented atypical clinical manifestations such as cognitive impairment (21.42%) and epileptic seizures (14.28%). Full recovery was found in 53.84% of all symptomatic episodes. After a mean follow-up of 43 months, recurrent PL episodes were seldom observed (21.42%), the annualized relapse rate was 0.95 and the mean final Expanded Disability Status Scale score was 1.5. The majority of PLs were supratentorial, coexisted with typical demyelinating plaques and showed the ring-like morphology and the ring pattern of contrast enhancement. Three patients had more than one PL on the same scan, all of the lesions with similar morphology., Conclusions: Our findings contribute to a better characterization of pseudotumoral forms of MS. However, larger studies are required to define this atypical entity more exactly., (© 2014 S. Karger AG, Basel.)

Background/objectives: Some experimental data suggest a possible role of tau protein in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. The aim of this study was to investigate a possible influence of the SNP rs1052553 in the MAPT gene in the risk for relapsing bout onset (relapsing-remitting and secondary progressive) MS., Methods: We analyzed the allelic and genotype frequency of MAPT rs1052553, which has been associated with some neurodegenerative diseases, in 259 patients with relapsing bout onset MS and 291 healthy controls, using TaqMan Assays., Results: MAPT rs1052553 allelic and genotype frequencies did not differ significantly between relapsing bout onset MS patients and controls, and were unrelated with the age of onset of MS or gender., Conclusions: These results suggest that MAPT rs1052553 polymorphism is not related with the risk for relapsing bout onset MS., (Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)