Actinomycetes Associated with Arthropods as a Source of New Bioactive Compounds.

Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the drug industry pipeline. Different strategies have been pursued to increase the chances of discovering new molecules, such as studying underexplored environments like arthropod symbionts, which represent a relevant reservoir for active metabolites. This review summarizes recent research on the identification of bioactive molecules produced by Actinomycetes associated with arthropods' microbiome. The metabolites have been categorized based on their structural properties and host, highlighting that multidisciplinary approaches will be the key to fully understanding this complex relationship.

Sex significantly predicts medial temporal volume when controlling for the influence of ApoE4 biomarker and demographic variables: A cross-ethnic comparison.

OBJECTIVE: To explore the relationship between age, education, sex, and ApoE4 (+) status to brain volume among a cohort with amnestic mild cognitive impairment (aMCI). METHOD: One hundred and twenty-three participants were stratified into Hispanic (n = 75) and White non-Hispanic (WNH, N = 48). Multiple linear regression analyses were conducted with age, education, sex, and ApoE4 status as predictor variables and left and right combined MRI volumes of the hippocampus, parahippocampus, and entorhinal cortex as dependent variables. Variations in head sizes were corrected by normalization with a total intracranial volume measurement. RESULTS: Bonferroni-corrected results indicated that when controlling for ApoE4 status, education, and age, sex was a significant predictor of hippocampal volume among the Hispanic group (ß = .000464, R2 = .196, p < .01) and the WNH group (ß = .000455, R2 = .195, p < .05). Education (ß = .000028, R2 = .168, p < .01) and sex (ß = .000261, R2 = .168, p < .01) were significant predictors of parahippocampal volume among the Hispanic MCI group when controlling for the effects of ApoE4 status and age. One-way ANCOVAs comparing hippocampal and parahippocampal volume between males and females within groups revealed that females had significantly larger hippocampal volumes (p < .05). Hispanic females had significantly larger hippocampal (p < .001) and parahippocampal (p < .05) volume compared to males. No sex differences in parahippocampal volume were noted among WNHs. CONCLUSIONS: Biological sex, rather than ApoE4 status, was a greater predictor of hippocampal volume among Hispanic and WNH females. These findings add to the mixed literature on sex differences in dementia research and highlight continued emphasis on ethnic populations to elucidate on neurodegenerative disparities.

ANISE: an application to design mechanobiology simulations of planar epithelia.

SUMMARY: TiFoSi (Tissues Forces & Signaling) is an efficient computational tool for performing mechanobiology simulations of planar epithelia. A drawback of this tool is that it relies on an XML configuration file (input data) that can be cumbersome to set up and/or decode due to the endless possibilities of the software. Moreover, some modeling know-how is needed in order to provide equations that describe gene regulatory interactions. These factors limit the usability of this tool for users with a weak computational and/or mathematical background. Here, we introduce ANISE (grAphical coNfigurator of TiFoSi In Silico Experiments), a web-app that allows to easily setup the configuration of mechanobiology simulations using TiFoSi. The application covers all the configuration modules in TiFoSi comprehensively (from basic to advanced editing options) and uses a graphical approach (e.g. to build the modeling equations of gene regulatory networks). AVAILABILITY AND IMPLEMENTATION: http://github.com/lsym-uveg/anise (server: http://lsymserver.uv.es/lsym/ANISE).

Corrected analysis of "the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial" that accounts for clustering and nesting verifies conclusions.

In this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.

Polymorphisms in the oxytocin receptor and their association with apathy and impaired social cognition in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive, motor, and neuropsychiatric manifestations. Oxytocin is a neuropeptide studied for its role as a neuromodulator regulating multiple behaviors linked to social cognition. Genetic variation of oxytocin receptor (OXTR) might interact in the etiology and development of several impaired social behaviors. Our aim was to study OXTR polymorphisms and their relationship with apathy and social cognition in HD. METHODS: OXTR was sequenced in 21 cases and 22 controls. We assessed apathy, anxiety, depression, and irritability (Hospital Anxiety and Depression Scale-Snaith Irritability scale, HADS-SIS) and social cognition (Ekman 60 faces test), motor symptoms and functionality with the total functional capacity (TFC), and the Unified HD rating Scale (UHDRS). RESULTS: We identified ten variants in OXTR. Three variants were classified as possibly damaging (p.Arg40Gly) or probably damaging (p.Leu46Pro, p.Thr102Asn). Subjects carrying the wild-type genotype of the synonymous variant p.Val45 showed a significantly lower score in the HADS-SIS scale, related to lower irritability (p = 0.013). The only subject carrying the heterozygous genotype of the synonymous variant p.Leu62 showed a significantly higher score on Ekman scale, compared to wild-type (p = 0.049); however, this finding was not confirmed after bootstrapping. CONCLUSION: Variations in OXTR could have a relevant role in the correct development of social and cognitive functions. Future approaches will include the molecular study of p.Arg40Gly, p.Leu46Pro, and p.Thr102Asn to confirm their pathogenicity, as well as the validation of the influence of p.Val45 and p.Leu62 variants for their involvement in irritability and social cognition in HD.

R-Ras1 and R-Ras2 Expression in Anatomical Regions and Cell Types of the Central Nervous System.

Since the optic nerve is one of the most myelinated tracts in the central nervous system (CNS), many myelin diseases affect the visual system. In this sense, our laboratory has recently reported that the GTPases R-Ras1 and R-Ras2 are essential for oligodendrocyte survival and maturation. Hypomyelination produced by the absence of one or both proteins triggers axonal degeneration and loss of visual and motor function. However, little is known about R-Ras specificity and other possible roles that they could play in the CNS. In this work, we describe how a lack of R-Ras1 and/or R-Ras2 could not be compensated by increased expression of the closely related R-Ras3 or classical Ras. We further studied R-Ras1 and R-Ras2 expression within different CNS anatomical regions, finding that both were more abundant in less-myelinated regions, suggesting their expression in non-oligodendroglial cells. Finally, using confocal immunostaining colocalization, we report for the first time that R-Ras2 is specifically expressed in neurons. Neither microglia nor astrocytes expressed R-Ras1 or R-Ras2. These results open a new avenue for the study of neuronal R-Ras2's contribution to the process of myelination.

Associations Between Country where Education is Obtained and Cognitive Functioning Among South American and Caribbean Older Adults Living in the U.S.

The increasing prevalence of AD among Hispanics calls for a need for examining factors that affect cognitive functioning and risk of AD among Hispanic older adults. The current study examined cognitive functioning among older Hispanic adults living in the U.S. from two Hispanic regions, South America and the Caribbean, in relation to the country where education was obtained. Participants (n = 139) were stratified into groups based on Hispanic education region and diagnostic categories: cognitively normal and amnestic MCI (aMCI). Results of Pearson correlations showed that among Hispanic Americans in general, there were significant positive correlations between the country of education to performance on measures of episodic, verbal, and word list tests. When examined separately by region and diagnosis, only cognitively normal (CN) South Americans showed significant relationships between country of education and cognitive functioning in these areas. Results of general linear models controlling for education identified differences in neuropsychological performance between groups with the CN groups demonstrating better performance than the aMCI groups within each region. Overall, it was evident that relationships between years of education obtained outside of the U.S. and cognitive functioning were not similar among individuals from these two disparate Spanish speaking regions. This is the first study to examine the country where education was obtained among individuals from countries located in different regions with different cultures that may influence their education and cognitive development throughout life. Findings contribute to the cross-cultural neuropsychological literature in understanding factors that are unique to Hispanic older adults at risk for developing AD.

HCP5 rs2395029 is a rapid and inexpensive alternative to HLA-B*57:01 genotyping to predict abacavir hypersensitivity reaction in Spain.

Abacavir (ABC) is an HIV nucleotide-analogue reverse transcriptase inhibitor that can produce a severe hypersensitivity reaction (ABC-HSR) in about 5% of the patients. The HLA-B*57:01 allele is associated with the development of ABC-HSR. Therefore, HLA-B*57:01 genotyping is required prior to the prescription of ABC. The technique routinely used in our laboratory is the sequence-specific oligonucleotide probes (SSOP) reverse hybridization method followed by Sanger sequencing. This technique is time-consuming and expensive. The single-nucleotide polymorphism (SNP) HCP5 rs2395029 was described to be in complete linkage disequilibrium with HLA-B*57:01. In this study, we aimed to assess the linkage disequilibrium between HCP5 rs2395029 and HLA-B*57:01 in patients receiving medical assistance at our hospital. We selected 226 HIV-infected patients from our hospital who had been routinely genotyped since 2009 with the SSOP and Sanger sequencing method: 49 HLA-B*57:01 positives and 177 negatives. We genotyped them for HCP5 rs2395019 by real time PCR (qPCR). We exploratory performed two copy number variation assays flanking HCP5 rs2395019 to explore possible deletions that could break the linkage disequilibrium with HLA-B*57:01. The concordance between HLA-B*57:01 and the HCP5 rs2395029 G allele was absolute, with a specificity and sensitivity of 100% (95% confidence interval: 93.0-100.0% and 98.0-100.0%, respectively) and estimated positive and negative predictive values of 84.4% (48.1-93.9%) and 99.9% (99.4-100.0%), respectively. No deletions were found at HCP5 flanking regions. The duration and cost of the SSOP-based method was considerably higher than the SNP-based method. Therefore, the HCP5 rs2395029 genotyping method may be alternatively used in the clinical practice.

The Utility of Cognitive Screeners in the Detection of Dementia Spectrum Disorders in Spanish-Speaking Populations.

Increasing rates of dementia spectrum disorders among Spanish-speaking geriatric populations necessitate the development of culturally appropriate cognitive screening tests that can identify neurodegenerative disorders in their earliest stages when emerging disease-modifying treatments are most likely to be effective. This scoping review identified 26 brief Spanish language cognitive screening tools (<20 minutes) by searching academic databases using a combination of search terms. Results suggest that the Mini-Mental Status Examination and Montreal Cognitive Assessment appear to be less valid than other screeners. Instruments such as the 7-Minute Screen and Mini-Cog evidence higher classification rates of dementia, while Phototest detected mild cognitive impairment at higher rates more consistently than other screeners. Different sensitivity and specificity outcomes and cutoffs were observed when the same cognitive screener was evaluated in different countries. Results indicate that it is imperative to increase nation-specific validation and normative data for these instruments to best serve diverse populations.

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial.

OBJECTIVE: To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. METHODS: Twenty-four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12-lead electrocardiogram were measured in supine position. AEs were also recorded. RESULTS: ARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs. CONCLUSIONS: OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.

Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as first-line therapy for the treatment of HIV infection. Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition. Dose adjustment based on G516T variant has been shown to be beneficial. However, this variant cannot explain the entire variability of efavirenz pharmacokinetics. In this study, we evaluated the influence of 11 single-nucleotide polymorphisms (SNPs) in CYP2B6, CYP2A6, CYP3A and ABCB1 (ATP-binding cassette sub-family B member 1) on the pharmacokinetics and safety of efavirenz after single oral dose administration to 47 healthy volunteers. We designed and validated a CYP2B6 activity score model based on two CYP2B6 SNPs (G516T and rs4803419) that predicted efavirenz disposition better than G516T alone.

The effects of aripiprazole and olanzapine on pupillary light reflex and its relationship with pharmacogenetics in a randomized multiple-dose trial.

AIMS: Pupillography is a noninvasive and cost-effective method to determine autonomic nerve activity. Genetic variants in cytochrome P450 (CYP), dopamine receptor (DRD2, DRD3), serotonin receptor (HTR2A, HTR2C) and ATP-binding cassette subfamily B (ABCB1) genes, among others, were previously associated with the pharmacokinetics and pharmacodynamics of antipsychotic drugs. Our aim was to evaluate the effects of aripiprazole and olanzapine on pupillary light reflex related to pharmacogenetics. METHODS: Twenty-four healthy volunteers receiving 5 oral doses of 10 mg aripiprazole and 5 mg olanzapine tablets were genotyped for 46 polymorphisms by quantitative polymerase chain reaction. Pupil examination was performed by automated pupillometry. Aripiprazole, dehydro-aripiprazole and olanzapine plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Aripiprazole affected pupil contraction: it caused dilatation after the administration of the first dose, then caused constriction after each dosing. It induced changes in all pupillometric parameters (P < .05). Olanzapine only altered minimum pupil size (P = .046). Polymorphisms in CYP3A, HTR2A, UGT1A1, DRD2 and ABCB1 affected pupil size, the time of onset of constriction, pupil recovery and constriction velocity. Aripiprazole, dehydro-aripiprazole and olanzapine pharmacokinetics were significantly affected by polymorphisms in CYP2D6, CYP3A, CYP1A2, ABCB1 and UGT1A1 genes. CONCLUSIONS: In conclusion, aripiprazole and its main metabolite, dehydro-aripiprazole altered pupil contraction, but olanzapine did not have such an effect. Many polymorphisms may influence pupillometric parameters and several polymorphisms had an effect on aripiprazole, dehydro-aripiprazole and olanzapine pharmacokinetics. Pupillography could be a useful tool for the determination of autonomic nerve activity during antipsychotic treatment.

Comparative Analysis of Kinect-Based and Oculus-Based Gaze Region Estimation Methods in a Driving Simulator.

Driver's gaze information can be crucial in driving research because of its relation to driver attention. Particularly, the inclusion of gaze data in driving simulators broadens the scope of research studies as they can relate drivers' gaze patterns to their features and performance. In this paper, we present two gaze region estimation modules integrated in a driving simulator. One uses the 3D Kinect device and another uses the virtual reality Oculus Rift device. The modules are able to detect the region, out of seven in which the driving scene was divided, where a driver is gazing at in every route processed frame. Four methods were implemented and compared for gaze estimation, which learn the relation between gaze displacement and head movement. Two are simpler and based on points that try to capture this relation and two are based on classifiers such as MLP and SVM. Experiments were carried out with 12 users that drove on the same scenario twice, each one with a different visualization display, first with a big screen and later with Oculus Rift. On the whole, Oculus Rift outperformed Kinect as the best hardware for gaze estimation. The Oculus-based gaze region estimation method with the highest performance achieved an accuracy of 97.94%. The information provided by the Oculus Rift module enriches the driving simulator data and makes it possible a multimodal driving performance analysis apart from the immersion and realism obtained with the virtual reality experience provided by Oculus.

R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System.

Rapid and effective neural transmission of information requires correct axonal myelination. Modifications in myelination alter axonal capacity to transmit electric impulses and enable pathological conditions. In the CNS, oligodendrocytes (OLs) myelinate axons, a complex process involving various cellular interactions. However, we know little about the mechanisms that orchestrate correct myelination. Here, we demonstrate that OLs express R-Ras1 and R-Ras2. Using female and male mutant mice to delete these proteins, we found that activation of the PI3K/Akt and Erk1/2-MAPK pathways was weaker in mice lacking one or both of these GTPases, suggesting that both proteins coordinate the activity of these two pathways. Loss of R-Ras1 and/or R-Ras2 diminishes the number of OLs in major myelinated CNS tracts and increases the proportion of immature OLs. In R-Ras1-/- and R-Ras2-/--null mice, OLs show aberrant morphologies and fail to differentiate correctly into myelin-forming phenotypes. The smaller OL population and abnormal OL maturation induce severe hypomyelination, with shorter nodes of Ranvier in R-Ras1-/- and/or R-Ras2-/- mice. These defects explain the slower conduction velocity of myelinated axons that we observed in the absence of R-Ras1 and R-Ras2. Together, these results suggest that R-Ras1 and R-Ras2 are upstream elements that regulate the survival and differentiation of progenitors into OLs through the PI3K/Akt and Erk1/2-MAPK pathways for proper myelination.SIGNIFICANCE STATEMENT In this study, we show that R-Ras1 and R-Ras2 play essential roles in regulating myelination in vivo and control fundamental aspects of oligodendrocyte (OL) survival and differentiation through synergistic activation of PI3K/Akt and Erk1/2-MAPK signaling. Mice lacking R-Ras1 and/or R-Ras2 show a diminished OL population with a higher proportion of immature OLs, explaining the observed hypomyelination in main CNS tracts. In vivo electrophysiology recordings demonstrate a slower conduction velocity of nerve impulses in the absence of R-Ras1 and R-Ras2. Therefore, R-Ras1 and R-Ras2 are essential for proper axonal myelination and accurate neural transmission.

A Physiological Sensor-Based Android Application Synchronized with a Driving Simulator for Driver Monitoring.

In this paper, we present an Android application to control and monitor the physiological sensors from the Shimmer platform and its synchronized working with a driving simulator. The Android app can monitor drivers and their parameters can be used to analyze the relation between their physiological states and driving performance. The app can configure, select, receive, process, represent graphically, and store the signals from electrocardiogram (ECG), electromyogram (EMG) and galvanic skin response (GSR) modules and accelerometers, a magnetometer and a gyroscope. The Android app is synchronized in two steps with a driving simulator that we previously developed using the Unity game engine to analyze driving security and efficiency. The Android app was tested with different sensors working simultaneously at various sampling rates and in different Android devices. We also tested the synchronized working of the driving simulator and the Android app with 25 people and analyzed the relation between data from the ECG, EMG, GSR, and gyroscope sensors and from the simulator. Among others, some significant correlations between a gyroscope-based feature calculated by the Android app and vehicle data and particular traffic offences were found. The Android app can be applied with minor adaptations to other different users such as patients with chronic diseases or athletes.

Sex differences in the development of mild cognitive impairment and probable Alzheimer's disease as predicted by hippocampal volume or white matter hyperintensities.

This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer's Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300-0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012-19.08]; HR = 4.665, 95% CI [1.072-20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166-0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011-1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.

Histone modifications associated with biological drug response in moderate-to-severe psoriasis.

INTRODUCTION: Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate-to-severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies. OBJECTIVE: To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM-SPSS v.23. RESULTS AND CONCLUSIONS: Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Non-significant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non-responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and non-responders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients' response to biological drugs in psoriasis.

Sperm count and motility are quantitatively affected by functional polymorphisms of HTR2A, MAOA and SLC18A.

Spermatozoa and neurones share similar membrane characteristics and features. Associations of multiple polymorphisms traditionally related to neurotransmission were investigated. Infertile men were grouped into controls with normospermia (n = 182) and idiopathic infertile men with asthenozoospermia (n = 103), and analysed as a case-control study and as a quantitative association of each genotype. Ten neurotransmission-associated genetic variants were mapped by SNP analysis using quantitative polymerase chain reaction with TaqMan probes. Men with HTR2A rs6313 had a higher risk of asthenozoospermia (OR = 2.14; P = 0.04). MAOA rs3788862 G carriers displayed an increased risk of asthenozoospermia (OR = 2.29; P = 0.02). The SLC18A1 rs1390938 G allele was more frequent among such cases (0.75 versus 0.87; P < 0.01 and P < 0.01 for Armitage trend test); for SLC18A1 rs2270641 P = 0.02 (case-control frequency) and P = 0.01 (Armitage trend test). MAOA rs3788862 was correlated with sperm motility (Spearman ρ = 0.14; P = 0.02); SLC18A1 rs1390938 was correlated with sperm count and motility (Spearman ρ = 0.20; P < 0.01). Gene polymorphisms of HTR2A, MAOA and SLC18A1, related to neurotransmission, are individually associated with asthenozoospermia through variation in sperm count and motility, without detectable allelic or genotype interaction.

Development of a method for the determination of 8-iso-PGF2α in sheep and goat plasma using solid-phase microextraction and ultra-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Isoprostane 8-iso-PGF2α is a biomarker of lipid peroxidation in cell membranes. The method developed to measure plasma total levels (esterified + free) of 8-iso-PGF2α must be reproducible and be able to reduce the use of solvents in solid phase extraction. It should be useful to evaluate oxidative stress due to the excess of free radicals that are generated by some disorder or disease. METHODS: The method was developed using solid-phase microextraction with Oasis®MAX µElution plates and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS). Electrospray ionization was performed in the negative mode (ESI-); the multiple reaction monitoring mode (MRM) was used. The development of the method included the optimization of the chromatographic conditions to achieve the separation of PGF2α and 8-iso-PGF2α as well as the optimization of the microextraction conditions of the analyte of interest in ovine and goat plasma. RESULTS: The developed method was validated with a calibration curve of plasma samples fortified with standards at five concentration levels in the range 49-639 pg/mL. The average recovery was 89% with a standard deviation of 10.73%. The inter-day precision was evaluated, obtaining a coefficient of variance (CV) less than 15%. The limit of quantification was 20 pg/mL and the limit of detection was 10 pg/mL. 8-iso-PGF2a was determined in the plasma of 14 sheep and 20 goats of 5 months of age and 6 goats of 24 months of age. The concentrations found were 50-300 pg/mL. CONCLUSIONS: The method developed is precise, accurate and reliable with low reagent consumption compared with conventional solid-phase extraction. The analysis time was decreased because, with the use of the microextraction plate, the step of the evaporation and reconstitution of the analyte was avoided. The method is applicable to quantify the plasma total levels (esterified + free) of 8-iso-PGF2α.