Can Glatiramer Acetate Prevent Cognitive Impairment by Modulating Oxidative Stress in Patients with Multiple Sclerosis?

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and neuroinflammation, often accompanied by cognitive impairment. This study aims (1) to investigate the potential of glatiramer acetate (GA) as a therapy for preventing cognitive decline in patients with MS (pwMS) by modulating oxidative stress (OS) and (2) to seek out the differences in cognition between pwMS in a cohort exhibiting good clinical evolution and control subjects (CS). An exploratory, prospective, multicentre, cross-sectional case-control study was conducted, involving three groups at a 1:1:1 ratio-41 GA-treated pwMS, 42 untreated pwMS, and 42 CS. The participants performed a neuropsychological battery and underwent venepuncture for blood sampling. The inclusion criteria required an Expanded Disability Status Scale score of ≤3.0 and a minimum of 5 years of MS disease. Concerning cognition, the CS had a better performance than the pwMS (p = <0.0001), and between those treated and untreated with GA, no statistically significant differences were found. Regarding oxidation, no statistically significant differences were detected. Upon categorizing the pwMS into cognitively impaired and cognitively preserved groups, the lactate was elevated in the pwMS with cognitive preservation (p = 0.038). The pwMS exhibited a worse cognitive performance than the CS. The pwMS treated with GA did not show an improvement in oxidation. Lactate emerged as a potential biomarker for cognitive preservation.

Mapping the literature on the qualitative approach to childhood asthma from 1996 to 2018: a bibliometric analysis / Mapeo de la literatura sobre el enfoque cualitativo del asma infantil desde 1996 hasta 2018: un análisis bibliométrico

Resumo Objectives: to describe the scientific production of qualitative studies in childhood asthma. Methods: bibliometric analysis. Articles were from Web of Science, Scopus, Cochrane, and PubMed (1996-2018), using the search terms asthma, children, qualitative research, qualitative study, qualitative analysis, ethnographic, phenomenology and narrative. Results: 258 articles were retrieved from 143 journals, representing 1.2% of scientific articles on childhood asthma. The growth rate was high. Authorship included 969 authors (85.3% occasional) from 279 institutions. 94.2% were co-authored and 3.5% were international collaborations. The greatest number of articles were from the United States (45.3%), United Kingdom (17.4%) and Canada (7.4%). The categories with the highest number of articles were Nursing & Public, Environmental & Occupational Health (18.2%), Respiratory System (10.1%) and Allergy (7.7%). 99.7% of the articles were in English. Conclusion: these results show a lack of consolidation of the literature based on qualitative studies on childhood asthma with a high percentage of occasional authors and limited international collaboration, indicating a need to strengthen this approach.

Resumen Objetivos: describir la producción científica de los estudios cualitativos sobre el asma infantil. Métodos: análisis bibliométrico. Los artículos procedían de Web of Science, Scopus, Cochrane y PubMed (1996-2018), utilizando los términos de búsqueda asthma, children, qualitative research, qualitative study, qualitative analysis, ethnographic, phenomenology y narrative. Resultados: se recuperaron 258 artículos de 143 revistas, lo que representa el 1,2% de los artículos científicos sobre asma infantil. La tasa de crecimiento fue elevada. La autoría incluyó 969 autores (85,3% ocasionales) de 279 instituciones. El 94,2% fueron coautores y el 3,5% colaboraciones internacionales. El mayor número de artículos procedió de Estados Unidos (45,3%), Reino Unido (17,4%) y Canadá (7,4%). Las categorías con mayor número de artículos fueron Enfermería y Salud Pública, Ambiental y Ocupacional (18,2%), Aparato Respiratorio (10,1%) y Alergia (7,7%). El 99,7% de los artículos estaban en inglés. Conclusión: estos resultados muestran una falta de consolidación de la literatura basada en estudios cualitativos sobre el asma infantil, con un alto porcentaje de autores ocasionales y una limitada colaboración internacional, lo que indica la necesidad de reforzar este enfoque.

Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Colaboración científica de Colombia con países de América Latina y del Caribe sobre la COVID-19 durante 2020 y 2021 / Colombia´s scientific collaboration with Latin American and Caribbean countries on COVID-19 during 2020 and 2021

Introducción: La necesidad de información por desconocimiento del Sars-CoV-2 llevó a los investigadores a generar una gran cantidad de información. Colombia es el segundo país latinoamericano con mayor producción científica sobre el Sars- CoV-2. Objetivo: caracterizar la tendencia de colaboración científica de Colombia con países de Latinoamérica y el Caribe sobre la COVID-19. Materiales y métodos: estudio bibliométrico, los registros se obtuvieron de Scopus (2020 - 2021) con los términos COVID-19, 2019-nCoV, new coronavirus, coronavirus disease 2019 y Sars-CoV-2. Se analizaron indicadores de producción, colaboración y visibilidad. Resultados: se recuperaron 77 registros. La tasa de crecimiento de la producción fue del 65,51 %. El índice de transitoriedad alcanzó el 86,69 %. El autor más productivo fue A.J. Rodríguez Morales de la Fundación Universitaria Autónoma de las Américas y Universidad Tecnológica de Pereira de Colombia (14,28 %). El 96,10 % de las investigaciones procedieron de universidades. La tasa de colaboración inter-latinoamericana alcanzó el 11,66 % con un índice de colaboración de 3,71 ± 3,09. La densidad de la red fue de 0,51. La mayor colaboración se dio con autores de México (n= 27), Perú (n= 26), Chile (n= 25) y Argentina (n= 23). Argentina presentó un mayor outdegree (176) y número de citas (55,03) y Chile un eigenvector superior (0,35). La correlación entre el número de citas y el grado de centralidad fue de 0,9. Conclusión: Colombia tiende a participar en proyectos internacionales y con países de Latinoamérica y el Caribecon mayor capacidad para desarrollar investigaciones.

Introduction: The need for information due to ignorance of Sars-CoV-2 led researchers to write and publish a large amount of information. Colombia is the second within Latin American countries with the highest scientific production on Sars- CoV-2. Objective: to characterize the trend of scientific collaboration between Colombia and Latin American and Caribbean countries on COVID-19. Materials and methods: bibliometric study, the records were acquired from Scopus (2020 - 2021) with the terms COVID-19, 2019-nCoV, new coronavirus, coronavirus disease 2019 and Sars-CoV-2. Indicators of production, collaboration and visibility were analyzed. Results: 77 records were recovered. The production growth rate was 65.51%. The transience index reached 86.69%. The most productive author was A.J. Rodríguez Morales of the Autonomous University Foundation of the Americas and the Technological University of Pereira of Colombia (14.28%). 96.10% of the investigations came from universities. The inter-Latin American collaboration rate reached 11.66% with a collaboration index of 3.71 ± 3.09. The density of the network was 0.51. The greatest collaboration occurred with authors from Mexico (n= 27), Peru (n= 26), Chile (n= 25) and Argentina (n= 23). Argentina presented a higher degree of improvement (176) and number of citations (55.03) and Chile a higher eigenvector (0.35). The connection between the number of citations and the degree of centrality was 0.9. Conclusion: Colombia tends to participate in international projects and with Latin America and the Caribbeancountries with greater capacity to develop research.

Glycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord. Glial cells, including astrocytes and microglia, have been shown to contribute to neurodegeneration in ALS, and metabolic dysfunction plays an important role in the progression of the disease. Glycogen is a soluble polymer of glucose found at low levels in the central nervous system that plays an important role in memory formation, synaptic plasticity, and the prevention of seizures. However, its accumulation in astrocytes and/or neurons is associated with pathological conditions and aging. Importantly, glycogen accumulation has been reported in the spinal cord of human ALS patients and mouse models. In the present work, using the SOD1G93A mouse model of ALS, we show that glycogen accumulates in the spinal cord and brainstem during symptomatic and end stages of the disease and that the accumulated glycogen is associated with reactive astrocytes. To study the contribution of glycogen to ALS progression, we generated SOD1G93A mice with reduced glycogen synthesis (SOD1G93A GShet mice). SOD1G93A GShet mice had a significantly longer life span than SOD1G93A mice and showed lower levels of the astrocytic pro-inflammatory cytokine Cxcl10, suggesting that the accumulation of glycogen is associated with an inflammatory response. Supporting this, inducing an increase in glycogen synthesis reduced life span in SOD1G93A mice. Altogether, these results suggest that glycogen in reactive astrocytes contributes to neurotoxicity and disease progression in ALS.

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies.

BACKGROUND: Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. METHODS: In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. RESULTS: DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. CONCLUSIONS: After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent ß-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in vitro and in vivo. CV-N neutralizes Delta and Omicron variants in vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains.

Análisis bibliométrico de los 100 artículos más citados publicados en español de Latinoamérica y el Caribe sobre COVID-19

El objetivo del estudio fue identificar los 100 artículos más citados sobre COVID-19 procedentes de Latinoamérica y el Caribe, publicados en español. Los registros se obtuvieron de la Web of Science. Se examinó: número de citas, autoría, cobertura geográfica, colaboración, revista y categorías temáticas. Los 100 artículos se publicaron en 41 revistas. La revista más citada fue Salud Pública de México (10 artículos; 75 citas). México fue el máximo exponente (28 artículos; 201 citas). Los autores más citados fueron: C. Alpuche-Aranda y E. Lazcano-Ponce, afiliados a la institución más citada, el Instituto Nacional de Salud Pública de México (n= 7). La principal categoría de la Web of Science fue Medicine, General & Internal (36 artículos; 173 citas). Epidemiología fue el tema más trabajado. No hubo correlación entre la colaboración internacional y el mayor número de citas (r= 0,15, p= 0,1). El estudio puede ayudar a reconocer la visibilidad de las investigaciones más citadas.

The aim of the study was to identify the 100 most cited articles on COVID-19 from Latin America and the Caribbean, published in Spanish. The records were obtained from the Web of Science. The following were examined: number of citations, authorship, geographic coverage, collaboration, journal and thematic categories. The 100 articles were published in 41 journals. The most cited journal was Salud Pública de México (10 articles; 75 citations). Mexico was the top performer (28 articles; 201 citations). The most cited authors were: C. Alpuche-Aranda and E. Lazcano-Ponce, affiliated with the most cited institution, the National Institute of Public Health of Mexico (n= 7). The main Web of Science category was Medicine, General & Internal (36 articles; 173 citations). Epidemiology was the most worked topic. There was no correlation between international collaboration and the highest number of citations (r= 0.15, p= 0.1). The study may help to recognize the visibility of the most cited research.

A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers.

To evaluate senescence mechanisms, including senescence-associated secretory phenotype (SASP), in the motor neuron disease model hSOD1-G93A, we quantified the expression of p16 and p21 and senescence-associated ß-galactosidase (SA-ß-gal) in nervous tissue. As SASP markers, we measured the mRNA levels of Il1a, Il6, Ifna and Ifnb. Furthermore, we explored whether an alteration of alternative splicing is associated with senescence by measuring the Adipor2 cryptic exon inclusion levels, a specific splicing variant repressed by TAR DNA-binding protein (TDP-43; encoded by Tardbp). Transgenic mice showed an atypical senescence profile with high p16 and p21 mRNA and protein in glia, without the canonical increase in SA-ß-gal activity. Consistent with SASP, there was an increase in Il1a and Il6 expression, associated with increased TNF-R and M-CSF protein levels, with females being partially protected. TDP-43 splicing activity was compromised in this model, and the senolytic drug Navitoclax did not alter the disease progression. This lack of effect was reproduced in vitro, in contrast to dasatinib and quercetin, which diminished p16 and p21. Our findings show a non-canonical profile of senescence biomarkers in the model hSOD1-G93A.

Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies.

Background: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. Methods: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. Results: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). Conclusions: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.

Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age.

Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)-as an anti-aging intervention-for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.

Acute ischemic stroke triggers a cellular senescence-associated secretory phenotype.

Senescent cells are capable of expressing a myriad of inflammatory cytokines and this pro-inflammatory phenomenon is known as senescence-associated secretory phenotype (SASP). The contribution of this phenomenon in brain ischemia was scarce. A mouse model of transient focal cerebral ischemia by compressing the distal middle cerebral artery (tMCAo) for 60 min was used. SASP, pro-inflammatory cytokines and cell cycle mRNAs levels were quantified at 30-min and 72 h post-surgery. Immunohistochemistry in paraffin embedded human brain slides and mouse brain tissue was performed. Our results showed an increase of both p16 and p21 mRNA restricted to the infarct area in the tMCAo brain. Moreover, there was an induction of Il6, Tnfa, Cxc11, and its receptor Cxcr2 mRNA pro-inflammatory cytokines with a high positive correlation with p16/p21 mRNA levels. The p16 was mainly shown in cytoplasm of neurons and cytoplasm/membrane of microglial cells. The p21 was observed in membrane of neurons and also it showed a mixed cytoplasmic and membranous pattern in the microglial cells. In a human stroke patient, an increase of P16 in the perimeter of the MCA infarct area was observed. These suggest a role of SASP in tMCAo mouse model and in human brain tissue. SASP potentially has a physiological role in acute ischemic stroke and neurological function loss.

Lipidomic traits of plasma and cerebrospinal fluid in amyotrophic lateral sclerosis correlate with disease progression.

Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain-an index of neuronal damage-were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P < 0.05; n = 27 for P < 0.01) than CSF (n = 17 for raw P < 0.05; n = 4 for P < 0.01), with almost no overlapping differential species, mainly characterized by an increased content of triacylglyceride species in plasma and decreased in CSF. Of note, false discovery rate correction indicated that one of the CSF lipids (monoacylglycerol 18:0) had high statistic robustness (false discovery rate-P < 0.01). Plasma lipidomes also varied significantly with the main involvement at onset (bulbar, spinal or respiratory). Notably, faster progression cases showed particular lipidome fingerprints, featured by decreased triacylclycerides and specific phospholipids in plasma, with 11 lipids with false discovery rate-P < 0.1 (n = 56 lipids in plasma for raw P < 0.01). Lipid species associated with progression rate clustered in a relatively low number of metabolic pathways, mainly triacylglyceride metabolism and glycerophospholipid and sphingolipid biosynthesis. A specific triacylglyceride (68:12), correlated with neurofilament content (r = 0.8, P < 0.008). Thus, the present findings suggest that systemic hypermetabolism-potentially sustained by increased triacylglyceride content-and CNS alterations of specific lipid pathways could be associated as modifiers of disease progression. Furthermore, these results confirm biochemical lipid heterogeneity in amyotrophic lateral sclerosis with different presentations and progression, suggesting the use of specific lipid species as potential disease classifiers.

Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment.

Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST, with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed a subcellular fractionation of the brain from transgenic mice overexpressing the Q331K-mutated TARDBP, and we analyzed the REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of the image analyses. TDP-43 aggregation was associated with alterations in the mRNA levels of the REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased the mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Furthermore, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes.

New insights into human prefrontal cortex aging with a lipidomics approach.

INTRODUCTION: Human prefrontal cortex (hPFC) is a recent evolutionarily developed brain region involved in cognitive functions. Human cognitive functions decline during aging. Yet the molecular mechanisms underlying the functional deterioration of the neural cells of this brain region still remain to be fully described. AREAS COVERED: In this review, we explore the role of lipids in hPFC aging. Firstly, we briefly consider the approaches used to identify lipid species in brain tissue with special attention paid to a lipidomics analysis. Then, as the evolution process has conferred a specific lipid profile on the hPFC, we consider the lipidome of hPFC. In addition, the role of lipids in hPFC aging, and in particular, the cognitive decline associated with aging, is discussed. Finally, nutritional and pharmacological interventions designed to modulate this process are examined. It is suggested that the dysfunction of key cellular processes secondarily to the damage of lipid membrane underlies the cognitive decline of hPFC during aging. EXPERT OPINION: Lipidomics methods are and will continue to be key tools in the effort to gain additional insights into the aging of the human brain.

Geographical distribution and international collaboration of Latin American and Caribbean scientific publications on tuberculosis in Pubmed. / Distribución geográfica y colaboración internacional de las publicaciones científicas latinoamericanas y del Caribe sobre tuberculosis en PubMed.

OBJECTIVE: The objective of the study was to describe the geographical coverage of Latin American and Caribbean scientific publications on tuberculosis and its international collaboration. MATERIALS AND METHODS: The records were retrieved from the PubMed database (2009-2018), limiting the search to Latin American and Caribbean countries. Articles were analyzed in several categories, such as the total number, countries, institutions, authors, collaborations, and citations. The software UCINET and VOSviewer were used. RESULTS: 2,495 items were recovered, 4.2% of world production. More than half of the research came from Brazil (52.5%), Mexico (16.6%) and Peru (10.5%). 97.6% of the production is co-authored, with a rate of international collaboration of 24.5%. The countries with the highest production in international collaboration are Brazil (39.1%), Peru (26.8%) and Mexico (16%); they are also the countries with the best OutDegree, OutCloseness and Betweenness. The United States (11.9%), United Kingdom (5.8%), France (2.1%), Spain and Switzerland (1.7%), South Africa (1.7%) and Italy (1.6%) are the main collaborators with Latin America. CONCLUSION: Brazil, together with Peru and Mexico, is the undisputed leader in Latin American and Caribbean tuberculosis production, due to the volume of articles and its position in the collaborative network. The eradication of tuberculosis requires continuing research in international collaboration, to carry out more effective health policies on tuberculosis.

OBJETIVO: Describir la cobertura geográfica de las publicaciones científicas de América Latina y el Caribe sobre tuberculosis y su colaboración internacional. MATERIALES Y MÉTODOS: Los registros fueron recuperados de la base de datos bibliográfica PubMed (2009-2018), limitando la búsqueda a países latinoamericanos y del Caribe. Los artículos se analizaron en varias categorías, como número total, países participantes, instituciones, autores, colaboraciones y citas. Se utilizó el software UCINET y VOSviewer para representar las redes de colaboración. RESULTADOS: Se recuperaron 2495 artículos, 4,2% de la producción mundial. Más de la mitad de las investigaciones proceden de Brasil (52,5%), México (16,6%) y Perú (10,5%). El 97,6% de la producción presenta coautoría, con una tasa de colaboración internacional del 24,5%. Los países con mayor producción en colaboración internacional son Brasil (39,1%), Perú (26,8%) y México (16%), además son los que presentan mejor centralidad, cercanía e intermediación. Estados Unidos (11,9%), Reino Unido (5,8%), Francia (2,1%), España y Suiza (1,7%), Sudáfrica (1,7%) e Italia (1,6%), son los principales colaboradores con Latinoamérica. CONCLUSIÓN: Brasil, junto a Perú y México, es líder de la producción científica sobre tuberculosis en Latinoamérica y el Caribe, por el volumen de artículos y su posición en la red de colaboración. La erradicación de la tuberculosis pasa por continuar investigando en colaboración internacional, y así llevar a cabo políticas de salud más efectivas en tuberculosis.

The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer's Disease Pathology.

Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer's disease (AD) pathology in the cerebrum. Compared with other cortical areas, the neurons from this brain region possess an inherent selective vulnerability derived from particular oxidative stress conditions that favor increased mitochondrial molecular damage with early bioenergetic involvement. This alteration of energy metabolism is the starting point for subsequent changes in a multitude of cell mechanisms, leading to neuronal dysfunction and, ultimately, cell death. These events are induced by changes that come with age, creating the substrate for the alteration of several neuronal pathways that will evolve toward neurodegeneration and, consequently, the development of AD pathology. In this context, the present review will focus on description of the biological mechanisms that confer vulnerability specifically to neurons of the entorhinal cortex, the changes induced by the aging process in this brain region, and the alterations at the mitochondrial level as the earliest mechanism for the development of AD pathology. Current findings allow us to propose the existence of an altered allostatic mechanism at the entorhinal cortex whose core is made up of mitochondrial oxidative stress, lipid metabolism, and energy production, and which, in a positive loop, evolves to neurodegeneration, laying the basis for the onset and progression of AD pathology.

Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study.

Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and age-matched controls. Lipidomic profiles of this subcellular fraction were obtained using liquid chromatography and mass spectrometry. We validated the mechanisms behind presumable lipidomic changes by exploring ALS surrogate models including human motor neurons (derived from ALS lines and controls) subjected to oxidative stress, the hSOD-G93A transgenic mice, and samples from an independent cohort of ALS patients. Among the differential lipid species, we noted 41 potential identities, mostly belonging to phospholipids (particularly ether phospholipids, as plasmalogens), as well as diacylglycerols and triacylglycerides. Decreased expression of alkyldihydroxyacetonephosphate synthase (AGPS)-a critical peroxisomal enzyme in plasmalogen synthesis-is found in motor neuron disease models; this occurs in parallel with an increase in the expression of sterol carrier protein 2 (SCP2) mRNA in ALS and Scp2 levels in G93A transgenic mice. Further, we identified diminished expression of diacylglycerol-related enzymes, such as phospholipase C ßI (PLCßI) and protein kinase CßII (PKCßII), linked to diacylglycerol metabolism. Finally, lipid droplets were recognized in the nuclei, supporting the identification of triacylglycerides as differential lipids. Our results point to the potentially pathogenic role of altered composition of nuclear membrane lipids and lipids in the nucleoplasm in the anterior horn of the spinal cord in ALS. Overall, these data support the usefulness of subcellular lipidomics applied to neurodegenerative diseases.

Distribución geográfica y colaboración internacional de las publicaciones científicas latinoamericanas y del Caribe sobre tuberculosis en PubMed / Geographical distribution and international collaboration of Latin American and Caribbean scientific publications on tuberculosis in Pubmed

RESUMEN Objetivo: Describir la cobertura geográfica de las publicaciones científicas de América Latina y el Caribe sobre tuberculosis y su colaboración internacional. Materiales y métodos: Los registros fueron recuperados de la base de datos bibliográfica PubMed (2009-2018), limitando la búsqueda a países latinoamericanos y del Caribe. Los artículos se analizaron en varias categorías, como número total, países participantes, instituciones, autores, colaboraciones y citas. Se utilizó el software UCINET y VOSviewer para representar las redes de colaboración. Resultados: Se recuperaron 2495 artículos, 4,2% de la producción mundial. Más de la mitad de las investigaciones proceden de Brasil (52,5%), México (16,6%) y Perú (10,5%). El 97,6% de la producción presenta coautoría, con una tasa de colaboración internacional del 24,5%. Los países con mayor producción en colaboración internacional son Brasil (39,1%), Perú (26,8%) y México (16%), además son los que presentan mejor centralidad, cercanía e intermediación. Estados Unidos (11,9%), Reino Unido (5,8%), Francia (2,1%), España y Suiza (1,7%), Sudáfrica (1,7%) e Italia (1,6%), son los principales colaboradores con Latinoamérica. Conclusión: Brasil, junto a Perú y México, es líder de la producción científica sobre tuberculosis en Latinoamérica y el Caribe, por el volumen de artículos y su posición en la red de colaboración. La erradicación de la tuberculosis pasa por continuar investigando en colaboración internacional, y así llevar a cabo políticas de salud más efectivas en tuberculosis.

ABSTRACT Objective: The objective of the study was to describe the geographical coverage of Latin American and Caribbean scientific publications on tuberculosis and its international collaboration. Materials and methods: The records were retrieved from the PubMed database (2009-2018), limiting the search to Latin American and Caribbean countries. Articles were analyzed in several categories, such as the total number, countries, institutions, authors, collaborations, and citations. The software UCINET and VOSviewer were used. Results: 2,495 items were recovered, 4.2% of world production. More than half of the research came from Brazil (52.5%), Mexico (16.6%) and Peru (10.5%). 97.6% of the production is co-authored, with a rate of international collaboration of 24.5%. The countries with the highest production in international collaboration are Brazil (39.1%), Peru (26.8%) and Mexico (16%); they are also the countries with the best OutDegree, OutCloseness and Betweenness. The United States (11.9%), United Kingdom (5.8%), France (2.1%), Spain and Switzerland (1.7%), South Africa (1.7%) and Italy (1.6%) are the main collaborators with Latin America. Conclusion: Brazil, together with Peru and Mexico, is the undisputed leader in Latin American and Caribbean tuberculosis production, due to the volume of articles and its position in the collaborative network. The eradication of tuberculosis requires continuing research in international collaboration, to carry out more effective health policies on tuberculosis.