Lipidomics signature in post-COVID patient sera and its influence on the prolonged inflammatory response.

BACKGROUND: The ongoing issues with post-COVID conditions (PCC), where symptoms persist long after the initial infection, highlight the need for research into blood lipid changes in these patients. While most studies focus on the acute phase of COVID-19, there's a significant lack of information on the lipidomic changes that occur in the later stages of the disease. Addressing this knowledge gap is critical for understanding the long-term effects of COVID-19 and could be key to developing personalized treatments for those suffering from PCC. METHODS: We employed untargeted lipidomics to analyze plasma samples from 147 PCC patients, assessing nearly 400 polar lipids. Data mining (DM) and machine learning (ML) tools were utilized to decode the results and ascertain significant lipidomic patterns. RESULTS: The study uncovered substantial changes in various lipid subclasses, presenting a detailed profile of the polar lipid fraction in PCC patients. These alterations correlated with ongoing inflammation and immune response. Notably, there were elevated levels of lysophosphatidylglycerols (LPGs) and phosphatidylethanolamines (PEs), and reduced levels of lysophosphatidylcholines (LPCs), suggesting these as potential lipid biomarkers for PCC. The lipidomic signatures indicated specific anionic lipid changes, implicating antimicrobial peptides (AMPs) in inflammation. Associations between particular medications and symptoms were also suggested. Classification models, such as multinomial regression (MR) and random forest (RF), successfully differentiated between symptomatic and asymptomatic PCC groups using lipidomic profiles. CONCLUSIONS: The study's groundbreaking discovery of specific lipidomic disruptions in PCC patients marks a significant stride in the quest to comprehend and combat this condition. The identified lipid biomarkers not only pave the way for novel diagnostic tools but also hold the promise to tailor individualized therapeutic strategies, potentially revolutionizing the clinical approach to managing PCC and improving patient care.

2-DE-based proteomic analysis of common bean (Phaseolus vulgaris L.) seeds.

Common bean (Phaseolus vulgaris L.) is the most important grain legume for direct human consumption. Proteomic studies in legumes have increased significantly in the last years but few studies have been performed to date in P. vulgaris. We report here a proteomic analysis of bean seeds by two-dimensional electrophoresis (2-DE). Three different protein extraction methods (TCA-acetone, phenol and the commercial clean-up kit) were used taking into account that the extractome can have a determinant impact on the level of quality of downstream protein separation and identification. To demonstrate the quality of the 2-DE analysis, a selection of 50 gel spots was used in protein identification by mass spectrometry (MALDI-TOF MS and MALDI-TOF/TOF). The results showed that a considerable proportion of spots (70%) were identified in spite of incomplete genome/protein databases for bean and other legume species. Most identified proteins corresponded to storage protein, carbohydrate metabolism, defense and stress response, including proteins highly abundant in the seed of P. vulgaris such as the phaseolin, the phytohemagglutinin and the lectin-related α-amylase inhibitor.

Integration of genome and phenotypic scanning gives evidence of genetic structure in Mesoamerican common bean (Phaseolus vulgaris L.) landraces from the southwest of Europe.

Southwestern Europe has been considered as a secondary centre of genetic diversity for the common bean. The dispersal of domesticated materials from their centres of origin provides an experimental system that reveals how human selection during cultivation and adaptation to novel environments affects the genetic composition. In this paper, our goal was to elucidate how distinct events could modify the structure and level of genetic diversity in the common bean. The genome-wide genetic composition was analysed at 42 microsatellite loci in individuals of 22 landraces of domesticated common bean from the Mesoamerican gene pool. The accessions were also characterised for phaseolin seed protein and for nine allozyme polymorphisms and phenotypic traits. One of this study's important findings was the complementary information obtained from all the polymorphisms examined. Most of the markers found to be potentially under the influence of selection were located in the proximity of previously mapped genes and quantitative trait loci (QTLs) related to important agronomic traits, which indicates that population genomics approaches are very efficient in detecting QTLs. As it was revealed by outlier simple sequence repeats, loci analysis with STRUCTURE software and multivariate analysis of phenotypic data, the landraces were grouped into three clusters according to seed size and shape, vegetative growth habit and genetic resistance. A total of 151 alleles were detected with an average of 4 alleles per locus and an average polymorphism information content of 0.31. Using a model-based approach, on the basis of neutral markers implemented in the software STRUCTURE, three clusters were inferred, which were in good agreement with multivariate analysis. Geographic and genetic distances were congruent with the exception of a few putative hybrids identified in this study, suggesting a predominant effect of isolation by distance. Genomic scans using both markers linked to genes affected by selection (outlier) and neutral markers showed advantages relative to other approaches, since they help to create a more complete picture of how adaptation to environmental conditions has sculpted the common bean genomes in southern Europe. The use of outlier loci also gives a clue about what selective forces gave rise to the actual phenotypes of the analysed landraces.

Informe sobre el ejercicio de estandarización de inmunofluorescencia indirecta (IFI) para la detección de anticuerpos antinucleares (ANA). Taller de autoinmunidad, Santander 2004 / Report on the indirect immunofluorescence (IFI) standardisation assay for the detection of antinuclear antibodies (ANA). Workshop on autoimmunity, Santander, May 2004

Para reducir las diferencias que se observan a la hora de titular por diferentes laboratorios un mismo suero ANA+, sugerimos el uso de unidades estándar. Con esta finalidad, en el presente Taller de Autoinmunidad, se distribuyeron cinco alícuotas de un mismo suero control, diluido seriadamente con PBS. A los laboratorios participantes se les pidió que diluyeran cada alícuota hasta su título final. Con estos datos se construyó una recta patrón para cada laboratorio. Además, se enviaron cuatro muestras problema. Estas muestras consistían en duplicados y diluciones de un mismo suero, con la finalidad de determinar si los laboratorios participantes eran capaces de replicar los duplicados y ordenar correctamente las diluciones. Los títulos remitidos para cada suero en diluciones se transformaron en unidades usando la curva patrón previamente obtenida por cada laboratorio. Los resultados obtenidos muestran que: 1) algunos laboratorios participantes no fueron capaces de replicar los duplicados o de ordenar adecuadamente las diluciones; 2) el uso de unidades en vez de diluciones disminuye la dispersión de los resultados obtenidos por los laboratorios participantes, para un suero dado. Por tanto, proponemos el uso de unidades estándar en lugar de diluciones cuando se informen títulos de ANA (AU)

El sistema inmunitario de las mucosas: una breve revisión / Mucosal immune system: a brief review

La mayoría de los antígenos que entran en contacto con el sistema inmune durante la vida de un ser vivo lo hacen a través de la superficie de la mucosa de los tractos respiratorio, gastrointestinal y urogenital. Ocupan una superficie de 400 m2 y forman el área de mayor tamaño en contacto directo con el ambiente externo. Las mucosas separan el ambiente externo del ambiente interno, estéril, y representan una primera línea de defensa. Esta barrera está en contacto tanto con patógenos que han desarrollado mecanismos eficaces para la colonización de epitelios e invasión de mucosas, como con antígenos inocuos, tales como comida, o la flora bacteriana comensal. En el primer caso se necesita una respuesta inmune eficaz y robusta, mientras que en el segundo se requiere una respuesta caracterizada por ignorancia o supresión activa. En estas condiciones, las mucosas han desarrollado un complejo sistema inmune, con características anatómicas y funcionales particulares, capaz de generar rigurosas respuestas frente a antígenos patogénicos, mientras mantiene una situación de ignorancia o supresión activa frente a antígenos no patogénicos (AU)

Higher proliferative capacity of T lymphocytes from patients with Crohn disease than from ulcerative colitis is disclosed by use of Herpesvirus saimiri-transformed T-cell lines.

BACKGROUND: T lymphocytes play a crucial role in the pathogenesis of inflammatory bowel disease. Achieving stable T-cell lines, rather than continuous bleeding of patients, is desirable in order to dissect their implication in the disease. METHODS: Long-lasting T-cell lines from patients with Crohn disease and ulcerative colitis and from healthy volunteers have been obtained by transformation of T lymphocytes using the lymphotropic Herpesvirus saimiri. Lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. RESULTS: Fresh cells revealed only minor differences between patients and controls, with regard to phenotype and proliferative capacity. In contrast, the use of T-cell lines showed that cells from Crohn disease patients, but not ulcerative colitis patients, over-responded to several membrane or cytoplasmic stimuli when compared to control T-cell lines. Thus, higher responses were found when stimulated with alphaCD3 and IL2, alphaCD3 and alphaCD28, IL2 alone, phorbol esters (PMA) and alphaCD3 and, finally, PMA and alphaCD2 (P < 0.05 in all instances). Further, lines from patients with Crohn disease responded more vigorously to alphaCD3 and alphaCD28 or alphaCD3 and PMA when compared to ulcerative colitis (P < 0.05 in both instances). CONCLUSIONS: The data obtained with these lines suggest that T cells from patients with Crohn disease differ in vivo in their proliferative capacity, as compared with those from ulcerative colitis patients, a finding that may reflect the clear Th-1 phenotype found in the former and absent in the latter.

[Late-onset Wilsons disease]. / Enfermedad de Wilson de manifestación tardía.

A 58-year old male with a past history of psychiatric disorders was studied for a persistent serum transaminase increase. Low serum ceruloplasmin level (lower than 3 mg/dL), increased urinary copper excretion, and increased liver tissue copper concentration (1050 mcg/g dry weight) confirmed the diagnosis of Wilsons disease. Slit lamp examination did not show Kayser-Fleischer rings. D-penicilamin therapy was followed by serum transaminase normalization. Similar late-onset cases of Wilsons disease are exceptional, but confirm the clinical heterogeneity of the disease.

Enfermedad de Wilson de manifestación tardía / Late-onset Wilson's disease

Un varón de 58 años con antecedente de trastornos psiquiátricos fue estudiado por elevación persistente de transaminasas. Se estableció el diagnóstico de enfermedad de Wilson en base a una ceruloplasmina sérica baja (menor de 3 mg/dL), una excreción urinaria de cobre aumentada y una concentración hepática de cobre aumentada (1050 mcg por gramo de tejido seco). No se observó anillo de Kayser-Fleischer en el estudio con lámpara de hendidura. Fue tratado con D-penicilamina, con normalización progresiva de las transaminasas. Los casos similares de enfermedad de Wilson de manifestación tardía son excepcionales, pero confirman la heterogeneidad clínica de la enfermedad. (AU)

Origin of Mayans according to HLA genes and the uniqueness of Amerindians.

The HLA allele frequency distribution of the Mayans from Guatemala was studied and compared with those of other First American Natives and worldwide populations (a total of 12,364 chromosomes and 6182 individuals from 60 different populations). The main conclusions were (1): the closest Amerindian group to Mayans is the Arhuacs, who were the first recorded Caribbean Islands' inhabitants (2). Mayans are not so close to Mesoamerican Zapotec, Mixe and Mixtec Amerindians, who genetically cluster together. Mixe had been related to Mayans only on linguistic bases (3). DRB1*0407 and DRB1*0802 alleles are found in 50% of Mayans; these alleles are also found in other Amerindians, but the Mayans' high frequencies may be showing a founder effect for this Mesoamerican-Caribbean population (4). Extended Mayan specific HLA haplotypes are described for the first time (5). Language and genes do not completely correlate in microgeographical studies (6). Significant genetic input from outside is not noticed in Meso and South American Amerindians according to the genetic analyses; while all world populations (including Africans, Europeans, Asians, Australians, Polynesians, North American Na-Dene Indians and Eskimos) are genetically related. Meso and South American Amerindians tend to remain isolated in the neighbour joining analyses.

Intrinsic defects explain altered proliferative responses of T lymphocytes and HVS-derived T-cell lines in gastric adenocarcinoma.

We have taken advantage of a recently described technique of transformation and immortalization of T lymphocytes using the lymphotropic Herpesvirus saimiri, to achieve long-lasting T-cell lines from gastric cancer patients and healthy volunteers. Blood samples were drawn and T lymphocytes were transformed. Once sustained growth was observed, lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. Cytofluorometric analysis revealed that CD3 and CD45 were found at lower proportion in primary cells from patients than from control individuals (54% vs 75%, p<0.001, 90% vs 96%, p<0.05, respectively), and in HVS-derived T-cell lines (90% vs 98%, p<0.05, 97% vs 100%, p<0.05, respectively). Proliferative analyses showed that primary isolated cells were unable to respond adequately to CD3-, CD2-, and PHA-mediated stimulation, as compared to controls. Similarly, T-cell lines from patients proliferated to a lesser extent when CD3- and CD2-mediated stimuli were considered, especially when simultaneous stimulation via CD3 and CD2 molecules was carried out (47,824 counts per minute [cpm] vs 121,478 cpm, p<0.05). Altogether these results show that the defects reported in T cells from patients with cancer are not exclusively due to tumour-derived factors, since the alterations persist in long-lasting, HVS-transformed, T-cell lines, suggesting that this model seems a suitable one to disclose them.

Influence of alcohol consumption on serum immunoglobulin E levels in atopic and nonatopic adults.

BACKGROUND: Total and specific serum immunoglobulin E (IgE) are routinely used as diagnostic tools in allergy clinics. Several studies have demonstrated an increase of total serum IgE concentrations in alcoholics, but the possible influence of lower quantities of ethanol intake on serum IgE values has not been fully evaluated. This study was aimed at analyzing the influence of alcohol intake on both total and specific serum IgE concentrations in patients studied in an allergy clinic. METHODS: A total of 460 patients were included in the study. According to skin-prick tests to common aeroallergens, 325 were classified as atopics and 135 as nonatopics. Most atopic patients (253; 78%) were allergic to mites. Alcohol consumption was recorded as the number of standard (10-g) drinking units regularly consumed per week. Two hundred subjects (43%) were abstainers, and 260 (57%) were regular consumers of a median of 30 g of alcohol per week. Total serum IgE was measured in all patients by latex-enhanced nephelometry. Serum-specific IgE was assayed by fluoroenzymeimmunoassay. RESULTS: Total serum IgE increased along with ethanol consumption. On multivariate analysis, regular alcohol consumption greater than 70 g per week was associated with increased total serum IgE levels, even when adjusting for age, sex, atopy, and smoking. Among house-dust mite-allergic patients, specific serum IgE values against the house dust mite Dermatophagoides pteronyssinus were higher in regular alcohol consumers than in abstainers. This difference was not observed among patients allergic to grass pollen (Lolium perenne). CONCLUSIONS: Alcohol consumption, even in moderate quantities, is associated with increased total and specific IgE concentrations in subjects studied in an allergy clinic. Alcohol intake should be taken into account in epidemiological studies of total serum IgE levels.

Allozyme evidence supporting southwestern Europe as a secondary center of genetic diversity for the common bean.

Genetic diversity within a common bean ( Phaseolus vulgaris L.) collection, comprising 343 accessions from the Iberian Peninsula, was examined using six allozyme markers. Two major clusters corresponding to the Andean and Mesoamerican gene pools were identified. Both gene pools were characterized by specific alleles, with the former exhibiting Skdh(100), Me(100), Rbcs(100 or 98) and Diap-1(100), and the latter exhibiting Skdh(103), Me(100), Rbcs(100) and Diap-1(95). Some accessions from both clusters, deviating from these allozyme patterns, exhibited Skdh(100), Me(100), Rbcs(100) and Diap-1(95) or Skdh(103), Me(100), Rbcs(100) and Diap-1(100) allozyme profiles and were considered as putative hybrids.The levels of genetic variation has not been eroded since the introduction of the common bean from the American centers of domestication to the Iberian Peninsula. Instead, obvious signs of introgression between the two gene pools were observed, mainly among white-seeded genotypes. The intermediate forms adapted to the Iberian Peninsula could have emerged from initial recombination between Mesoamerican and Andean gene pools. The Iberian common bean germplasm is therefore more complex than previously thought, and contains additional diversity that remains to be explored for genetic and breeding purposes. The Iberian Peninsula could be considered as a secondary center of genetic diversity of the common bean, especially the large white-seeded genotypes.

Prevalence of liver disease in patients with Streptococcus bovis bacteraemia.

BACKGROUND: The relationship between Streptococcus bovis bacteraemia and gastrointestinal disease (mainly colon cancer) is well known. Patients with advanced liver disease are prone to bacteraemia. Less attention has been paid to the association between liver disease and Streptococcus bovis bacteraemia in the literature. AIMS: To evaluate the prevalence of liver disease in patients with S. bovis bacteraemia. PATIENTS AND METHODS: Twenty-two episodes of S. bovis bacteraemia in 20 adults (13 males and seven females, with a median age of 61 years, range 32-94 years) were detected in a single hospital over a 7-year period. Ten of them had endocarditis. Patients' clinical records were reviewed, with special focus on underlying liver and gastrointestinal disease. RESULTS: Eleven patients (55%) had a chronic liver disease. Nine of them were cirrhotics. Ten patients had a history of chronic alcohol abuse, and four patients had hepatitis C virus antibodies (associated with alcohol abuse in three cases). Large bowel disease was present in six out of 13 evaluable patients (adenocarcinoma in three cases). Patients with liver disease were younger than patients without it. Mortality related to S. bovis bacteraemia was particularly high among patients with advanced liver disease (Child-Pugh state C). Bacteraemia recurred two times in one alcoholic cirrhotic, who was diagnosed as having a Dukes-B colon cancer 4.5 years after the first episode of S. bovis bacteraemia. CONCLUSIONS: In our area, S. bovis bacteraemia is frequently associated with chronic liver disease. Liver disease may be a predisposing factor for S. bovis bacteraemia.

[Upper digestive tract findings in elderly patients with iron-deficiency anemia. A comparison between users and non-users of non-steroidal anti-inflammatory drugs]. / Patología digestiva alta en pacientes de edad avanzada con anemia ferropénica: comparación entre usuarios y no usuarios de anti-inflamatorios no esteroideos.

BACKGROUND: Iron-deficiency anemia is common in the elderly. Chronic upper gastrointestinal bleeding is its most frequent cause. The use of non-steroidal antinflammatory drugs (NSAID) is common in older people. Gastrointestinal complications of NSAID may be also more frequent among the elderly. AIMS: The study was aimed to evaluate if a history of regular NSAID use in elderly patients with iron-deficiency anemia is associated to characteristic findings on esophagogastroduodenoscopy. MATERIALS AND METHODS: A total of 91 patients (40% of males and 60% females) older than 65 years (mean age 77 years, range 65-90 years) entered the study. All of them had been admitted to our Hospital for study of iron-deficiency anemia. Thirty-eight patients were regular users of NSAID. Esophagogastroduodenoscopy was performed in all patients. RESULTS: The prevalences of peptic ulcer, erosive gastritis/duodenitis, and esophagitis were similar in NSAID users and non-users (13 vs 11%, 18 vs 15%, and 26 vs 26%, respectively). A trend to a higher prevalence of gastric adenocarcinoma was observed the group of NSAID non-users (8% vs 23%, p = 0.05). Esophagogastroduodenoscopy was entirely normal in 39% of NSAID users and 34% of NSAID non-users. CONCLUSIONS: Upper gastrointestinal lesions in elderly patients with iron-deficiency anemia are similar in NSAID users and non-users, with the exception of gastric adenocarcinoma which can be more common in NSAID non-users.

Increased serum IgE in alcoholics: relationship with Th1/Th2 cytokine production by stimulated blood mononuclear cells.

BACKGROUND: Increased serum immunoglobulin (Ig) E values are frequently found in alcoholics. Cytokines produced by T-helper-2 (Th2) lymphocytes are required for IgE synthesis. Chronic alcoholism is associated with altered cytokine balance. This study analyzed the relationship between Th1 and Th2 cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) and serum IgE levels, both in atopic and nonatopic alcoholics. METHODS: Twenty-five patients admitted to the hospital with alcohol withdrawal syndrome were included in the study. Five were classified as atopic and 20 as nonatopic by means of skin-prick tests. Interleukin-4 (IL-4), IL-10, IL-12, IL-13, and interferon gamma were measured in the supernatants of 48-hr cultures of PBMCs stimulated with phytohemagglutinin. Total serum IgE was measured by chemiluminescent enzyme immunoassay. Results were compared with those of 15 healthy controls (seven atopics and eight nonatopics). RESULTS: Total serum IgE concentrations were higher in alcoholics than in controls, in both atopic and nonatopic subjects. The ratio of IL-4 to interferon gamma production by phytohemagglutinin-stimulated PBMCs (as an approach to Th2/Th1 balance) was significantly lower in alcoholics than in healthy controls, both in the atopic and in the nonatopic group. No difference was observed regarding IL-10, IL-12, and IL-13 production between alcoholics and controls. No correlation was demonstrated between cytokine production and total serum IgE levels in any group. CONCLUSIONS: Increased total serum IgE is observed in alcoholics together with a paradoxically low ratio of Th2 to Th1 cytokine production by phytohemagglutinin-stimulated PBMCs. These findings are independent of the atopic status of patients.

Patología digestiva alta en pacientes de edad avanzada con anemia ferropénica: comparación entre usuarios y no usuarios de anti-inflamatorios no esteroideos / Upper digestive tract findings in elderly patients with iron-deficiency anemia. a comparison between users and non-users of non-steroidal anti-inflamma tory drugs

Antecedentes: La anemia ferropénica es frecuente en el anciano, y su causa más frecuente es el sangrado gastrointestinal crónico. En los ancianos es muy común el uso de anti-inflamatorios no esteroideos (AINEs). Las complicaciones gastrointestinales del uso de AINES son más frecuentes en los sujetos de edad avanzada. Objetivos: El estudio fue dirigido a analizar si el uso habitual de AINEs en pacientes ancianos con anemia ferropénica se asocia a mayor prevalencia de determinadas lesiones en la endoscopia digestiva alta.Materiales y métodos: Se incluyeron 91 pacientes (40 por ciento varones y 60 por ciento mujeres) mayores de 65 años (edad media 77 años, rango 65-90 años). Todos habían sido ingresados en el hospital por anemia ferropénica. Un total de 38 pacientes eran usuarios habituales de AINES. Se realizó endoscopia digestiva alta en todos los casos.Resultados: Las prevalencias de úlcera péptica, gastritis o duodenitis erosiva y esofagitis fueron similares en usuarios y no usuarios de AINEs (13 vs 11 por ciento, 18 vs 15 por ciento, y 26 vs 26 por ciento, respectivamente). La proporción de pacientes con adenocarcinoma gástrico fue mayor en el grupo de no usuarios de AINEs (8 por ciento vs 23 por ciento, p=0.05). La endoscopia digestiva alta fue enteramente normal en 39 por ciento de los usuarios de AINEs y en el 34 por ciento de los no usuarios.Conclusiones: Las lesiones en el tramo alto del aparato digestivo en pacientes de edad avanzada con anemia ferropénica son similares en usuarios y no usuarios de AINEa, con la excepción del adenocarcinoma gástrico, que puede ser más común en los no usuarios de AINEs. (AU)

Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12.

Cytokine balance alterations are responsible for some of the systemic and hepatic manifestations of alcoholism. The present study was aimed to evaluate the influence of both acute alcohol abstinence (in alcoholics) and acute alcohol intake (in healthy subjects) on serum IL-6, IL-8, IL-10, and IL-12 levels. Serum cytokine concentrations were determined on admission and after a median of 6 days of ethanol abstinence in 29 patients with alcohol withdrawal syndrome. The same determinations were made in five healthy volunteers at baseline and after 36 h of a single 60 g-dose alcohol intake. Increased serum levels of IL-6, IL-10 and, to a lesser extent IL-8, declined in the few days after alcohol abstinence in patients with alcohol withdrawal syndrome. Serum IL-8 values increased after alcohol intake in healthy subjects. Rapid variation of serum cytokine levels along with alcohol intake or abstinence should be taken into account in cytokine studies in alcohol abusers.