Immunomodulatory activity of argentatins A and B isolated from guayule.

Argentatins are secondary metabolites synthesized by guayule (Parthenium argentatum A. Gray) with numerous potential medical applications. In addition to inhibiting insect growth, they are endowed with several pharmacological properties including antimicrobial and antitumorigenic activity. However, their potential as immunomodulators remains unexplored. The aim of the present study was to investigate whether argentatins can modulate the function of the immune system. Human mesenchymal stem cells were treated with argentatins and the production of several anti- and proinflammatory cytokines was evaluated. The effect of argentatins on the polarization of CD4+ T-lymphocytes and macrophages was also assessed. Results demonstrated that argentatins can modulate the production of proinflammatory cytokines and the polarization of cellular phenotypes, including Th2 lymphocytes and M1 macrophages. These findings suggest that argentatins are promising therapeutic agents in autoimmune or allergic diseases, and open new perspectives for the investigation of argentatins in immune response and in the development of more targeted and effective immunomodulatory therapies.

New strategies to analyze argentatins A and B in guayule (Parthenium argentatum, A. Gray).

There is considerable interest in the exploitation of compounds belonging to the triterpenoid family from guayule (Parthenium argentatum, A. Gray), as they offer several beneficial effects to human health. The most abundant triterpenoids in guayule resin are the argentatins, which are currently analyzed by labor-intensive and time-consuming techniques. The purpose of the present study was to estimate argentatins and isoargentatins A and B in guayule using near-infrared spectroscopy (NIRS) and flow injection analysis (FIA). Results revealed that the best partial least squares regression model exhibited excellent correlation with the values estimated by NIRS calibration (r2c = 0.99-1.00) and cross-validation (r2cv = 0.94-0.99), and the residual predictive deviation was >3 in all cases. After optimization of the liquid chromatography-mass spectrometry and FIA parameters, the FIA mode could reliably collect data for argentatin A and B after applying a calculated coverage factor. In sum, NIRS and FIA appear to be a robust option for the estimation and routine analysis of argentatins in guayule stems and resin, respectively.

Consideraciones anestésicas para cesárea electiva en una paciente con quiste de Tarlov gigante / Anaesthetic considerations for elective cesarean section in a patient with a giant Tarlov cyst

Los quistes de Tarlov son una dilatación patológica de las meninges. Su incidencia es más frecuente en mujeres de edades comprendidas entre 30 y 50 años. La prueba de imagen de elección para su diagnóstico es la RM. De etiología desconocida, la mayoría de los casos son asintomáticos, pero pueden manifestarse síntomas de irritación radicular, entre otros. Las posibilidades terapéuticas son múltiples, reservando la escisión quirúrgica como último escalón. Presentamos un caso en el que se realiza con éxito una anestesia raquídea para una cesárea electiva en una paciente con un quiste de Tarlov gigante, pero con potencial compromiso de la vía aérea, en la que la que los riesgos de una anestesia general podrían estar aumentados. El manejo anestésico presenta un desafío para el anestesiólogo, especialmente en situaciones en las que el paciente presente un riesgo anestésico aumentado para la anestesia general, como es el caso de la paciente obstétrica.(AU)

Tarlov cysts are a pathological dilatation of the meninges. Their incidence is more frequent in women between 30 and 50 years of age. The imaging test of choice for diagnosis is MRI. Of unknown etiology, most cases are asymptomatic, but symptoms of radicular irritation, among others, may occur. The therapeutic possibilities are multiple, reserving surgical excision as the last option. We report a case of successful spinal anaesthesia for elective cesarean section in a patient with a giant Tarlov cyst but with potential airway compromise, in whom the risks of general anaesthesia would be increased. Anaesthetic management presents a challenge for the anesthesiologist, especially in situations where the patient presents an increased anaesthetic risk for general anaesthesia, as is the case in the obstetric patient.(AU)

Anaesthetic considerations for elective cesarean section in a patient with a giant Tarlov cyst.

Tarlov cysts are a pathological dilatation of the meninges. Their incidence is more frequent in women between 30 and 50 years of age. The imaging test of choice for diagnosis is MRI. Of unknown etiology, most cases are asymptomatic, but symptoms of radicular irritation, among others, may occur. The therapeutic possibilities are multiple, reserving surgical excision as the last option. We report a case of successful spinal anaesthesia for elective cesarean section in a patient with a giant Tarlov cyst but with potential airway compromise, in whom the risks of general anaesthesia would be increased. Anaesthetic management presents a challenge for the anesthesiologist, especially in situations where the patient presents an increased anaesthetic risk for general anaesthesia, as is the case in the obstetric patient.

Anti-Human Herpesvirus 6 A/B Antibodies Titers Correlate With Multiple Sclerosis-Associated Retrovirus Envelope Expression.

Human endogenous retrovirus W family envelope proteins (pHERV-W ENV/syncytin-1) have been repeatedly associated with multiple sclerosis (MS). Here, we have focused on the study of pHERV-W ENV/syncytin-1 expression levels in MS patients (relapsing and progressive forms) and in healthy donors (HD) and on exploring their possible relationship with Epstein-Barr virus (EBV) and human herpesvirus-6A/B (HHV-6A/B). We included blood samples from 101 MS patients and 37 HD to analyze antiviral antibody titers by ELISA and pHERV-W ENV/syncytin-1 expression levels by flow cytometry as well as by qPCR. Patients with relapsing MS forms showed significantly higher pHERV-W ENV/syncytin-1 protein and gene expression levels than HD. Progressive MS patients also showed significantly higher protein and gene expression levels than both HD and relapsing MS patients. Regarding antiviral antibodies titers, anti-HHV-6A/B IgM levels were positively correlated with pHERV-W ENV/syncytin-1 protein expression levels in patients with relapsing MS, while in the progressive forms patients this correlation was found with anti-HHVA/B IgG levels. Therefore, pHERV-W ENV could be involved in MS pathogenesis, playing a role in relapsing and progressive forms. Besides, anti-HHV-6A/B antibodies positively correlated with pHERV-W ENV expression. Further studies are needed to better understand this possible relationship.

Biological Activity of Extracts from Aromatic Plants as Control Agents against Spoilage Molds Isolated from Sheep Cheese.

The aim of this work was to assess the antifungal and antioxidant activity of essential oils and ethanolic extracts from distilled solid by-products from aromatic plants (Artemisia dracunculus, Hyssopus officinalis, Lavandula stoechas, Origanum vulgare and Satureja montana) against 14 fungi strains isolated from sheep cheese and identified at species level using DNA barcoding based on ß-tubulin sequence analysis. In addition, capacity of fungi to produce ochratoxin A, patulin, cyclopiazonic acid and sterigmatocystin was analyzed. Of the isolates, 85.7% belonged to Penicillium (P. commune/biforme, P. crustosum) and 14.3% to Aspergillus (A. puulaauensis and A. jensenii), the first time that these Aspergillus species have been found in sheep's cheese. All P. commune isolates were producers of cyclopiazonic acid, and the two Aspergillus strains produced sterigmatocystin, but the others did not produce any tested mycotoxin. Among the essential oils tested, oregano, savory and tarragon had a significant antifungal activity against all the isolated strains, but no ethanolic extract showed antifungal activity. By contrast, ethanolic extracts showed great potential as antioxidants. The identification of new molds in cheese will help the dairy industry to know more about those molds affecting the sector, and the use of aromatic plants in the control of fungal spoilage could be a suitable alternative to chemical preservatives used in the agri-food industry.

Effect of Seasonal Decrease in Temperature on the Content and Composition of Guayulins in Stems of Guayule (Parthenium argentatum, Gray).

The guayulins are a family of sesquiterpene compounds that consist of an isoprenoid nucleus substituted either by trans-cinnamic or p-anisic acid, and are present only in the resinous fraction of the rubber plant guayule (Parthenium argentatum, Gray). While the natural role of the guayulins remains enigmatic, they may serve as a defense function against other plants or herbivores by virtue of the accumulation of cinnamic acid. Prior research has suggested seasonal variation in guayulin content, which has been shown to decrease as winter arrives in two different varieties. In the present study, the effect of guayulins has been evaluated in 13 different accessions cultivated under the same conditions during autumn. A general reduction in guayulin content was found in the stems from all varieties between the September and November harvest, which was accompanied by an increase in the resin content. With respect to individual guayulins, while guayulin A was the most prominent member during most of the year, guayulin C had more prominence when temperature started to decrease. In this seasonal period, the production of each member of the guayulin family in the leaves was very balanced.

Adapting the Accelerated Solvent Extraction Method for Resin and Rubber Determination in Guayule Using the BÜCHI Speed Extractor.

Guayule (Parthenium argentatum Gray) is a promising alternative source to Hevea brasiliensis for the production of natural rubber, which can reach levels of 8-9% under industrialized farming conditions. The most common method for determining rubber concentration is by accelerated solvent extraction (ASE), a technique developed by the Dionex Corporation and almost exclusively performed with the Dionex ASE-200 or 350 systems. Herein, it is sought to apply and adapt the most common methods used in the literature for the Dionex system to another extraction platform, the BÜCHI Speed Extractor E-914. Results showed that using a sand sandwich method to confine the sample in the center and exploiting a larger cell volume (80 mL) for extraction prevents the occurrence of overpressure and problems with clogging. Under optimized conditions, the coefficient of variation was <15% for both resin quantification for samples containing 5.0-15.8% of resin and for rubber quantification for samples with 1.7-10.3% rubber content. The extraction time for resin (2 cycles of 5 min each) was smaller than for rubber (2 cycles of 20 min each). It would be interesting to carry out interlaboratory comparisons to standardize the method at an international level.

Fatal consequences of decreased sensitivity to pain and temperature in a frontotemporal dementia patient.

Frontotemporal dementia (FTD) is a heterogeneous syndrome characterized by the progressive damage of frontal and temporal brain regions. These networks largely overlap with those involved in pain and temperature processing. Although the impaired perception of pain and temperature has been previously described to be relatively common in patients with FTD, these symptoms are often not consistently assessed by Neurologists. We present the case of a patient with a probable behavioral variant FTD who died due to scalding with hot water in the shower. Impairments in the perception of pain and temperature might have played a fundamental role in this accident.

Spraying Ozonated Water on Bobal Grapevines: Effect on Wine Quality.

Ozonated water is being introduced as an alternative phytosanitary treatment to control grapevine diseases in a context in which the reduction of chemical pesticides has become an urgent necessity. In this study, we evaluated the effect of spraying grapevines with ozonated water on the enological, phenolic, and aromatic qualities of Bobal wines during two consecutive growing seasons. In the first season, ozonated water was applied once during the ripening period on grapevines trained on the traditional gobelet system (S1). In the second season, three applications were performed between fruit set and harvest on grapevines grown on a vertical trellis system (S2). The S1 treatment led to a wine with an increased alcoholic degree and a remarkably higher phenolic content, which resulted in preferable chromatic characteristics. The S2 treatment maintained the total phenolic content but significantly enhanced stilbenes and flavanols and also reduced anthocyanins, which negatively affected the wine colour. Regarding aroma, both treatments reduced the content of glycosylated precursors and had different effects on free volatiles, both varietal and fermentative. Thus, the metabolic response of grapevines to the ozonated water stress, and therefore the quality of wines, depended on the ozone dose received by the plants.

Spraying ozonated water on Bobal grapevines: Effect on grape quality.

Ozone is a powerful oxidant that is increasingly used as sanitizing agent in the wine industry and even in the vineyard to control grapevine diseases. In this study, we evaluated the effect on grape enological quality of ozonated water spraying treatments carried out in Bobal grapevines during two consecutive harvest seasons. In the first season, ozonated water was applied once during the ripening period on grapevines trained on the traditional gobelet system (S1). In the second season, ozonated water was applied three times between the fruit set and harvest on grapevines grown on a vertical trellis system (S2). Grape quality on harvest day was evaluated through several enological and chromatic parameters, the phenolic maturity, the Varietal Aroma Potential Index (IPAv) and the phenolic and volatile composition. The S1 treatment had a positive effect on the technological maturity, the chromatic parameters, the seed maturity and the content of glycosylated aroma precursors, phenolic compounds and free terpenoids of grapes. The S2 treatment also improved the technological maturity and the content of total anthocyanins (pH 1.0) and free terpenoids, but had a negative impact on the chromatic parameters, the anthocyanin extractability and the content of glycosylated aroma precursors and phenolic compounds. Therefore, ozonated water sprayed on Bobal grapevines affected the quality of grapes, but the effect seemed to depend on the number of applications.

An alternative approach to GTV margin determination in stereotactic body radiotherapy.

PURPOSE: This study aims to estimate a realistic margin in stereotactic body radiotherapy (SBRT) through examining the determination uncertainties of gross tumour volume (GTV). METHODS: Three computed tomography (CT) scans were performed on each patient in different sessions as a treatment simulation. Registration of the different CT image sets was based on the fiducial marks from two stereotactic guides. GTV was defined in each one of them, as well as both the encompassing (UNI) and overlapping (INT) volumes. This protocol was altered following imaging guided radiotherapy (IGRT) implementation, so tumour displacements could be corrected for. The patient was scanned without repositioning solely considering tumour intrafraction variations. In addition, isocentre and dimension variations were obtained for each patient and cohort. A Monte Carlo code was developed to simulate tumour volume, considering them as ellipsoids in order to study their behaviour. Lastly, the equivalent radius (R eq) was defined for each of these volumes, experimental and simulated, and both and values were derived by simple linear regression to the mean value . RESULTS: The global margin M can be defined as this systematic error plus an additional residual random uncertainty, with values M = 3.4 mm for Body Frame, M = 2.3 mm for BodyFIX and M = 2.1 mm without repositioning. The experimental results obtained are in good agreement with simulated values, validating the use of the Monte Carlo code to calculate a margin formula. CONCLUSIONS: Introducing IGRT is not enough to obtain a zero margin; consequently, the safety margin, dependent on tumour shape and size dispersion, can be evaluated using this formulation.

Internalizing Symptoms Mediate the Relation Between Acute Pain and Autism in Adults.

Research on pain in autism spectrum disorder (ASD) is in its infancy, with almost nothing known about how individual differences may predicting pain response in ASD. In the present study, 45 adults (28 male, age 22-48 years) with diagnoses of autism and intellectual delay were observed during vaccination or dental cleaning and their pain behaviours coded and measures of autism symptom severity, anxiety, depression and obsessivity taken. Our findings showed that greater autism severity predicted greater pain response which was partially mediated by anxiety and depression. These data suggest that mental health symptoms are important when considering pain response in autism. Mood must therefore be considered in future research on pain in ASD as well as clinical pain management.

Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis

Purpose: After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice. Methods/patients: We classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated. Results and conclusions: RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis

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Study of the possible link of 25-hydroxyvitamin D with Epstein-Barr virus and human herpesvirus 6 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Although the causes of multiple sclerosis (MS) remain partially unknown, environmental and genetic factors are thought to play a role in its aetiopathogenesis. Hypovitaminosis D, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) infections have been described as possible MS triggers. Our aim was to analyse the possible link between 25-hydroxyvitamin D [25(OH)D] and viruses in patients with MS. METHODS: We included 482 patients with MS in a 2-year study. Serum samples were collected to analyse 25(OH)D levels and, according to sample availability, antibody titres against EBV and HHV-6 by enzyme-linked immunosorbent assay. DNA was extracted from blood in order to analyse EBV and HHV-6 viral load by quantitative real-time polymerase chain reaction and to genotype MS-related single nucleotide polymorphisms (rs3135388, rs2248359 and rs12368653) when possible. RESULTS: The 25(OH)D levels were significantly higher in the first semester of the year than in the second. Carriers of the risk allele rs2248359-C showed lower 25(OH)D levels than non-carriers. For EBV, viral load was significantly higher when 25(OH)D levels were low, demonstrating an inverse correlation between 25(OH)D levels and EBV load. CONCLUSIONS: The 25(OH)D levels could be involved in the regulation of EBV replication/reactivation in patients with MS.

Leaching of polycyclic aromatic hydrocarbons (PAHs) from coal dumps reclaimed with apple trees: a mechanistic insight.

Polycyclic aromatic hydrocarbons (PAHs) have been identified as compounds that can be incorporated to run-off waters or to aquifers becoming a real threat not only to aquatic organisms but also to humans due to its carcinogenic and mutagenic activity. This work studies the presence of PAHs in a coal dump pile located in the north of Spain (Asturias), downhill a spoil pile of a cinabrium mine. This unique site gives the opportunity to assess whether acid waters have more potential to leach PAHs than normal rainwater (acidified when it gets in contact with coal spoil). The distribution of PAHs and methyl PAHs has shown that their abundance is higher in the path of acid waters which could be caused by the ability of acid water to break bonds of coal macromolecules. This chemical reaction liberates PAHs of less molecular weight that can be detected by GC-MS. Moreover, less soluble PAHs are concentrated on the acid water circulation area and more soluble PAHs more leached by acid water that rainwater, which indicates that PAHs dissolve more in acid waters than in normal rainwater. In addition, this coal spoil pile has been reclaimed with apple trees to make cider for human consumption. Up to 152 different compounds were identified in the tree samples, but neither PAHs nor methyl PAHs were found, pointing to a possible retention of the PAHs in the roots zone. Apple trees in the acid waters path show more concentration in waxes and flavour compounds, indicating a more mature apple.

Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis.

PURPOSE: After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice. METHODS/PATIENTS: We classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated. RESULTS AND CONCLUSIONS: RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.