Like mother like son: Transgenerational memory and cross-tolerance from drought to heat stress are identified in chloroplast proteome and seed provisioning in Pinus radiata.

How different stressors impact plant health and memory when they are imposed in different generations in wild ecosystems is still scarce. Here, we address how different environments shape heritable memory for the next generation in seeds and seedlings of Pinus radiata, a long-lived species with economic interest. The performance of the seedlings belonging to two wild clonal subpopulations (optimal fertirrigation vs. slightly stressful conditions) was tested under heat stress through physiological profiling and comparative time-series chloroplast proteomics. In addition, we explored the seeds conducting a physiological characterization and targeted transcriptomic profiling in both subpopulations. Our results showed differential responses between them, evidencing a cross-stress transgenerational memory. Seedlings belonging to the stressed subpopulation retained key proteins related to Photosystem II, chloroplast-to-nucleus signalling and osmoprotection which helped to overcome the applied heat stress. The seeds also showed a differential gene expression profile for targeted genes and microRNAs, as well as an increased content of starch and secondary metabolites, molecules which showed potential interest as biomarkers for early selection of primed plants. Thus, these finds not only delve into transgenerational cross-stress memory in trees, but also provide a new biotechnological tool for forest design.

Physical exercise improves memory in sedentary middle-aged adults: Are these exercise-induced benefits associated with S-Klotho and 1,25-dihydroxivitamin D? The FIT-AGEING randomized controlled trial.

We aimed to investigate the effect of three types of exercise interventions on memory (i.e., immediate memory (IM), long-term memory (LTM), and recognition). We also investigated whether exercise-induced changes in circulating S-Klotho and 1,25-dihydroxivitamin D (1,25(OH)2 D) levels were related to those observed in memory in healthy middle-aged sedentary adults. A 12-week randomized controlled trial was performed with a parallel-group design. Seventy-four participants (45-65 years old: 53% women) were randomly assigned to (1) no exercise (control) group, (2) concurrent training based on the international physical activity recommendations (PAR) group, (3) high-intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT-EMS) group. Memory outcomes were assessed using the Wechsler Memory Scale-third edition. S-Klotho plasma levels were determined according to a solid-phase sandwich enzyme-linked immunosorbent assay kit while 1,25(OH)2 D plasma levels were measured using a DiaSorin-Liaison immunochemiluminometric analyzer. IM-Verbal Paired Associates (IM-VPA) and IM-Logical Memory (IM-LM) were improved in both the HIIT and HIIT-EMS groups compared with the control group (all p ≤ 0.045). Exercise-induced changes in S-Klotho plasma levels were positively associated with those observed in IM, LTM, and recognition (all p ≤ 0.007), whereas exercise-induced changes in 1,25(OH)2 D plasma levels were directly related to changes in IM and LTM (all p ≤ 0.048). In conclusion, a 12-week HIIT intervention with or without WB-EMS seems to be the most effective exercise program to improve IM. The significant and positive associations between exercise-induced changes in S-Klotho and 1,25(OH)2 D levels with those observed in memory outcomes suggest that these factors may be potentially related to exercise-induced improvements of memory in middle-aged adults.

Biomarker metabolite mating of viable frozen-thawed in vitro-produced bovine embryos with pregnancy-competent recipients leads to improved birth rates.

Selection of competent recipients before embryo transfer (ET) is indispensable for improving pregnancy and birth rates in cattle. However, pregnancy prediction can fail when the competence of the embryo is ignored. We hypothesized that the pregnancy potential of biomarkers could improve with information on embryonic competence. In vitro-produced embryos cultured singly for 24 h (from d 6 to 7) were transferred to d 7 synchronized recipients as fresh or after freezing and thawing. Recipient blood was collected on d 0 (estrus; n = 108) and d 7 (4-6 h before ET; n = 107) and plasma was analyzed by nuclear magnetic resonance (1H+NMR). Spent embryo culture medium (CM) was collected and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry in a subset of n = 70 samples. Concentrations of metabolites quantified in plasma (n = 35) were statistically analyzed as a function of pregnancy diagnosed on d 40, d 62 and birth. Univariate analysis with plasma metabolites consisted of a block study with controllable fixed factors (i.e., embryo cryopreservation, recipient breed, and day of blood collection; Wilcoxon test and t-test). Metabolite concentrations in recipients and embryos were independently analyzed by iterations that reclassified embryos or recipients using the support vector machine. Iterations identified some competent embryos, but mostly competent recipients that had a pregnancy incompetent partner embryo. Misclassified recipients that could be classified as competent were reanalyzed in a new iteration to improve the predictive model. After subsequent iterations, the predictive potential of recipient biomarkers was recalculated. On d 0, creatine, acetone and l-phenylalanine were the most relevant biomarkers at d 40, d 62, and birth, and on d 7, l-glutamine, l-lysine, and ornithine. Creatine was the most representative biomarker within blocks (n = 20), with a uniform distribution over pregnancy endpoints and type of embryos. Biomarkers showed higher abundance on d 7 than d 0, were more predictive for d 40 and d 62 than at birth, and the pregnancy predictive ability was lower with frozen-thawed (F-T) embryos. Six metabolic pathways differed between d 40 pregnant recipients for fresh and F-T embryos. Within F-T embryos, more recipients were misclassified, probably due to pregnancy losses, but were accurately identified when combined with embryonic metabolite signals. After recalculation, 12 biomarkers increased receiver operator characteristic-area under the curve (>0.65) at birth, highlighting creatine (receiver operator characteristic-area under the curve = 0.851), and 5 new biomarkers were identified. Combining metabolic information of recipient and embryos improves the confidence and accuracy of single biomarkers.

Nucleus and chloroplast: A necessary understanding to overcome heat stress in Pinus radiata.

The recovery and maintenance of plant homeostasis under stressful environments are complex processes involving organelle crosstalk for a coordinated cellular response. Here, we revealed through nuclear and chloroplast subcellular proteomics, biochemical cell profiles and targeted transcriptomics how chloroplasts and nuclei developed their responses under increased temperatures in a long-lived species (Pinus radiata). Parallel to photosynthetic impairment and reactive oxygen species production in the chloroplast, a DNA damage response was triggered in the nucleus followed by an altered chromatin conformation. In addition, in the nuclei, we found several proteins, such as HEMERA or WHIRLY, which change their locations from the chloroplasts to the nuclei carrying the stress message. Additionally, our data showed a deep rearrangement of RNA metabolism in both organelles, revealing microRNAs and AGO1 as potential regulators of the acclimation mechanisms. Altogether, our study highlights the synchronisation among the different stages required for thermotolerance acquisition in P. radiata, pointing out the role of chromatin conformation and posttranscriptional gene regulation in overcoming heat stress and assuring plant survival for the following years.

Non-Invasive Identification of Sex in Cultured Bovine Embryos by UHPLC-MS/MS Metabolomics.

INTRODUCTION: Different gene expression between male and female bovine embryos leads to metabolic differences. OBJECTIVE: We used UHPLC-MS/MS to identify sex metabolite biomarkers in embryo culture medium (CM). METHODS: Embryos were produced in vitro under highly variable conditions, i.e., fertilized with 7 bulls, two breeds, and cultured with BSA or BSA + serum until Day-6. On Day-6, embryos were cultured individually for 24 h. CM of Day-7 embryos (86 female and 81 male) was collected, and Day-6 and Day-7 embryonic stages recorded. RESULTS: A study by sample subsets with fixed factors (culture, bull breed, and Day-6 and Day-7 stages) tentatively identified 31 differentially accumulated metabolites through 182 subsets. Day-6 and Day-7 stage together affected 13 and 11 metabolites respectively, while 19 metabolites were affected by one or another stage and/or day. Culture supplements and individual bull changed 19 and 15 metabolites, respectively. Single bull exerted the highest influence (20 metabolites with the significantly highest p values). Lipid (93 subsets; 11 metabolites) and amino acid (55 subsets; 13 metabolites) were the most relevant classes for sex identification. CONCLUSIONS: Single biomarker led to inefficient sex diagnosis, while metabolite combinations accurately identified sex. Our study is a first in non-invasive sex identification in cattle by overcoming factors that induce metabolic variation.

Multiomics Molecular Research into the Recalcitrant and Orphan Quercus ilex Tree Species: Why, What for, and How.

The holm oak (Quercus ilex L.) is the dominant tree species of the Mediterranean forest and the Spanish agrosilvopastoral ecosystem, "dehesa." It has been, since the prehistoric period, an important part of the Iberian population from a social, cultural, and religious point of view, providing an ample variety of goods and services, and forming the basis of the economy in rural areas. Currently, there is renewed interest in its use for dietary diversification and sustainable food production. It is part of cultural richness, both economically (tangible) and environmentally (intangible), and must be preserved for future generations. However, a worrisome degradation of the species and associated ecosystems is occurring, observed in an increase in tree decline and mortality, which requires urgent action. Breeding programs based on the selection of elite genotypes by molecular markers is the only plausible biotechnological approach. To this end, the authors' group started, in 2004, a research line aimed at characterizing the molecular biology of Q. ilex. It has been a challenging task due to its biological characteristics (long life cycle, allogamous, high phenotypic variability) and recalcitrant nature. The biology of this species has been characterized following the central dogma of molecular biology using the omics cascade. Molecular responses to biotic and abiotic stresses, as well as seed maturation and germination, are the two main objectives of our research. The contributions of the group to the knowledge of the species at the level of DNA-based markers, genomics, epigenomics, transcriptomics, proteomics, and metabolomics are discussed here. Moreover, data are compared with those reported for Quercus spp. All omics data generated, and the genome of Q. ilex available, will be integrated with morphological and physiological data in the systems biology direction. Thus, we will propose possible molecular markers related to resilient and productive genotypes to be used in reforestation programs. In addition, possible markers related to the nutritional value of acorn and derivate products, as well as bioactive compounds (peptides and phenolics) and allergens, will be suggested. Subsequently, the selected molecular markers will be validated by both genome-wide association and functional genomic analyses.

The rainbow protocol: A sequential method for quantifying pigments, sugars, free amino acids, phenolics, flavonoids and MDA from a small amount of sample.

The elucidation of plant health status requires quantifying multiple molecular metabolism markers. Until now, the extraction of these biomarkers is performed independently, with different extractions and protocols. This approach is inefficient, since it increases laboratory time, amount of sample, and could introduce biases or difficulties when comparing data. To limit these drawbacks, we introduce a versatile protocol for quantifying seven of the most commonly analysed biomarkers (photosynthetic pigments, free amino acids, soluble sugars, starch, phenolic compounds, flavonoids and malondialdehyde) covering substantial parts of plant metabolism, requiring only a minimum sample amount and common laboratory instrumentation. The procedures of this protocol rely on classic methods that have been updated to allow their sequential use, increasing reproducibility, sensibility and easiness to obtain quantitative results. Our method has been tested and validated over an extended diversity of organisms (Arabidopsis thaliana, Solanum lycopersicum, Olea europaea, Quercus ilex, Pinus pinaster and Chlamydomonas reinhardtii), tissues (leaves, roots and seeds) and stresses (cold, drought, heat, ultraviolet B and nutrient deficiency). Its application will allow increasing the number of parameters that can be monitored at once while decreasing sample handling and consequently, increasing the capacity of the laboratory.

Cardiometabolic Risk is Positively Associated with Underreporting and Inversely Associated with Overreporting of Energy Intake Among European Adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study.

BACKGROUND: Dietary misreporting is the main limitation of dietary assessments and has been associated with BMI during youth. However there are no prior studies assessing misreporting and cardiometabolic risks (CMRs) in adolescence. OBJECTIVES: To examine the associations between dietary misreporting and CMR factors in adolescents and to assess the potential bias in the association between CMR and energy intake (EI) driven by dietary misreporting. METHODS: Two 24-hour dietary recalls were obtained from 1512 European adolescents (54.8% girls) aged 12.5-17.5 years. Physical activity was measured by accelerometry. Cut-offs suggested by Huang were applied to identify misreporters. Height, waist circumference (WC), the sum of 4 skinfold thicknesses, diastolic blood pressure (DBP), systolic blood pressure (SBP), and cardiorespiratory fitness (CRF) measurements were taken and serum triglycerides and total-/high-density lipoprotein cholesterol ratio were analyzed. A sex- and age-specific clustered CMR score (n = 364) was computed. Associations were investigated by multilevel regression analyses adjusting for age, sex, center, socioeconomic status, and physical activity. RESULTS: Underreporting (24.8% adolescents) was significantly (P < 0.05) associated with a higher WC, waist-to-height ratio (WHeR), and sum of skinfold thickness, whereas overreporting (23.4% adolescents) was significantly associated with a lower WC, WHeR, sum of skinfold thickness, and SBP. Associations between CMR factors and EI were significantly affected by misreporting, considering various approaches. Significant, positive associations became inverse after adjusting for misreporting for WC and WHeR. The opposite was true for the sum of skinfold thickness, SBP, and CMR score. The associations between EI and DBP and CRF did not remain significant after adjusting for misreporting. CONCLUSIONS: CMR factors differed among misreporting groups, and both abdominal and total fat mass indicators were more strongly associated with all forms of misreporting than was BMI. Moreover, misreporting seems to bias EI and CMR associations in adolescents. Therefore, energy misreporting should be taken into account when examining diet-CMR associations.

Monitoring of pharmaceuticals in aquatic biota (Procambarus clarkii) of the Doñana National Park (Spain).

In this work the presence of different pharmaceuticals at Doñana National Park (Spain) and their main entry sources (input source or entry points) have been stated over the 2011-2016 years period. Twenty-three selected pharmaceuticals (corresponding to eight therapeutic families) were evaluated in crayfish and water samples from Doñana National Park (Spain) (six sampling points selected in order to cover different possible pollution sources into and surrounding the Park). The multiresidue determination was carried out using enzymatic-microwave assisted extraction prior to high performance liquid chromatography mass spectrometry detection. Sulphonamides (sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole); trimethoprim, an antibiotic that is frequently co-administered with sulfamethoxazole; amphenicols (chloramphenicol, florfenicol and thiamphenicol); fluoroquinolones (ciprofloxacin, enrofloxacin, flumequine, danofloxacin, gatifloxacin, norfloxacin, marbofloxacin and grepafloxacin); penicillins (amoxicillin); tetracyclines (chlortetracycline and oxytetracycline); non-steroidal anti-inflammatory drugs (salicylic acid and ibuprofen); beta-blocker drugs (atenolol); and antiepileptics (carbamazepine) were analysed. Ciprofloxacin, ibuprofen, salicylic acid, flumequine, and carbamazepine were detected and/or quantified at some of the selected sampling points. A clear ecotoxicological risk to the ecosystem was demonstrated from the occurrence of ciprofloxacin in samples obtained after the punctual and massive presence of people inside the Park. Furthermore, flumequine and carbamazepine have been detected in Procambarus clarkii specimens in concentrations around 30 ng g-1 and 14 ng g-1, respectively, and their occurrence in the specimens could indicate the persistence of the discharge sources. The main source of pharmaceuticals into the Park might be the livestock farming activities, and the influence of urban wastewaters from surrounding villages does not seem to be very important.

Exercise training improves sleep quality: A randomized controlled trial.

BACKGROUND: Exercise holds promise as a non-pharmacological intervention for the improvement of sleep quality. Therefore, this study investigates the effects of different training modalities on sleep quality parameters. MATERIAL & METHODS: A total of 69 (52.7% women) middle-aged sedentary adults were randomized to (a) control group, (b) physical activity recommendation from the World Health Organization, (c) high-intensity interval training (HIIT) and (d) high-intensity interval training group adding whole-body electromyostimulation training (HIITEMS). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) scale and accelerometers. RESULTS: All intervention groups showed a lower PSQI global score (all P < .022). HIIT-EMS group improved all accelerometer parameters, with higher total sleep time and sleep efficiency, and lower wake after sleep onset (all P < .016). No differences were found between groups in any sleep quality parameter. CONCLUSION: In conclusion, exercise training induced an improvement in subjective sleep quality in sedentary middleaged adults. Moreover, HIIT-EMS training showed an improvement in objective sleep quality parameters (total sleep time, sleep efficiency and wake after sleep onset) after 12 weeks of exercise intervention. The changes observed in the HIIT-EMS group were not statistically different to the other exercise modalities.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

Direct capillary electrophoresis analysis of basic and acidic drugs from microliter volume of human body fluids after liquid-phase microextraction through nano-fibrous membrane.

In the present work, a disposable microextraction device with a polyamide 6 nano-fibrous supported liquid membrane (SLM) is employed for the pretreatment of minute volumes of biological fluids. The device is placed in a sample vial for an at-line coupling to a commercial capillary electrophoresis instrument with UV-Vis detection (CE-UV) and injections are performed fully automatically from the free acceptor solution above the SLM with no contact between the capillary and the membrane. Up to 4-fold enrichment of model basic (nortriptyline, haloperidol, loperamide, and papaverine) and acidic (ibuprofen, naproxen, ketoprofen, and diclofenac) drugs is achieved by optimizing the ratio of the donor to the acceptor solution volumes (16 to 4 µL, respectively). The actual setup enables SLM extractions from less than a drop of sample and is suitable for pretreatment of scarce human body fluids. Two unique methods are reported for efficient clean-up and enrichment of the basic and acidic drugs from capillary blood (formed as dried blood spot), serum, and urine samples, which enable their determination at therapeutic and/or toxic levels. The hyphenation of the SLM extraction with CE-UV analysis provides good repeatability (RSD, 2.4-14.9%), linearity (r2, 0.988-1.000), sensitivity (LOD, 0.017-0.22 mg L-1), and extraction recovery (ER, 20-106%) at short extraction times (10 min) and with minimum consumption of samples and reagents. Graphical abstract.

On-chip electromembrane extraction of acidic drugs.

In the present work, a new supported liquid membrane (SLM) has been developed for on-chip electromembrane extraction of acidic drugs combined with HPLC or CE, providing significantly higher stability than those reported up to date. The target analytes are five widely used non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), diclofenac (DIC), naproxen (NAX), ketoprofen (KTP) and salicylic acid (SAL). Two different microchip devices were used, both consisted basically of two poly(methyl methacrylate) (PMMA) plates with individual channels for acceptor and sample solutions, respectively, and a 25 µm thick porous polypropylene membrane impregnated with the organic solvent in between. The SLM consisting of a mixture of 1-undecanol and 2-nitrophenyl octyl ether (NPOE) in a ratio 1:3 was found to be the most suitable liquid membrane for the extraction of these acidic drugs under dynamic conditions. It showed a long-term stability of at least 8 hours, a low system current around 20 µA, and recoveries over 94% for the target analytes. NPOE was included in the SLM to significantly decrease the extraction current compared to pure 1-undecanol, while the extraction properties was almost unaffected. Moreover, it has been successfully applied to the determination of the target analytes in human urine samples, providing high extraction efficiency.

Proteomics, Holm Oak (Quercus ilex L.) and Other Recalcitrant and Orphan Forest Tree Species: How do They See Each Other?

Proteomics has had a big impact on plant biology, considered as a valuable tool for several forest species, such as Quercus, Pines, Poplars, and Eucalyptus. This review assesses the potential and limitations of the proteomics approaches and is focused on Quercus ilex as a model species and other forest tree species. Proteomics has been used with Q. ilex since 2003 with the main aim of examining natural variability, developmental processes, and responses to biotic and abiotic stresses as in other species of the genus Quercus or Pinus. As with the progress in techniques in proteomics in other plant species, the research in Q. ilex moved from 2-DE based strategy to the latest gel-free shotgun workflows. Experimental design, protein extraction, mass spectrometric analysis, confidence levels of qualitative and quantitative proteomics data, and their interpretation are a true challenge with relation to forest tree species due to their extreme orphan and recalcitrant (non-orthodox) nature. Implementing a systems biology approach, it is time to validate proteomics data using complementary techniques and integrate it with the -omics and classical approaches. The full potential of the protein field in plant research is quite far from being entirely exploited. However, despite the methodological limitations present in proteomics, there is no doubt that this discipline has contributed to deeper knowledge of plant biology and, currently, is increasingly employed for translational purposes.

Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival.

Cardiac involvement (CI) is a known complication of SSc associated with increased mortality. Our objective was to describe a cohort of patients with SSc and CI and to assess the differences between cutaneous subsets regarding their presentation and survival. Three hundred and ninety-three Spanish patients from a single center, diagnosed with SSc, were retrospectively studied for evidence of CI using noninvasive and invasive tests from 1976 to 2011. Clinical, epidemiological, immunological and therapeutic features of patients with CI were compared to those without it and within the different cutaneous subsets of SSc. CI was present in 173 (44 %) patients. Mitral regurgitation (67 %), conduction alterations (45 %) and left ventricle diastolic dysfunction (40 %) were the most common findings. Pericardial involvement and heart failure were more frequent in diffuse SSc (dcSSc) than in limited or sine scleroderma SSc. CI accounted for 20 % of deaths, and it was an independent mortality risk factor (HR 2.1, P = 0.02), but once CI was established, classical dcSSc mortality risk factors determined mortality. Patients with dcSSc developed CI faster than limited (HR 1.9, P = 0.003) or sine SSc patients (HR 2.5, P = 0.002), specially during the first year after SSc onset. We found statistically significant differences between the 3 SSc subsets in the presentation of pericardial involvement and heart failure. CI increased the mortality and appeared at a higher rate, especially during the first year after SSc onset. Screening for heart involvement should be performed at diagnosis and during follow-up.

Agar films containing silver nanoparticles as new supports for electromembrane extraction.

A new support containing silver nanoparticles to assist electromembrane extraction (EME) procedures is proposed. For the first time, synthesized agar films containing silver nanoparticles (AgNPs) have been used as a support for liquid membranes in EME. Agarose films of 20 µm thickness containing 107.9 mg Ag/g agar were synthesized and characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM), showing isolated spherical silver nanoparticles of 20-30 nm diameter with homogeneous distribution. Nanometallic films were cut and glued to narrow bore glass tubes and used as supports for a dihexyl ether liquid membrane for use in an EME procedure. EME conditions were optimized and applied to the extraction of selected non-steroidal anti-inflammatory drugs (NSAIDs). The results were compared to those using polypropylene membranes (450 µm and 100 µm thickness), achieving 10- to 70-fold higher extraction efficiency. This article opens a new line of research into electrically assisted microextraction systems by combining other possible kinds of nanometallic films, including different metals, film functionalization through metallic NPs, and the use of low polarity solvents. Also, very low currents are obtained during the extraction process, which lead to high electromigration of the analytes.

Clinical Features and Disease Activity in Psoriatic Arthritis: A Sex-Related Perspective on Leptin and Comorbidity.

Background/Objectives: Many studies have addressed the sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying these differences. The aims of our study were to assess the presence of clinical features in relation to sex, and to measure the effect on disease activity of different comorbidities in each sex. Methods: This was a cross-sectional study in which the following factors were measured: the clinical features of the disease, disease activity, the physical function and the disease impact. We measured serum leptin levels, to eliminate the effect of obesity on leptin levels, and a leptin/BMI ratio was calculated. The comorbid conditions evaluated included anxiety and depression, and sleep quality. Results: A total of 203 patients participated in this study. The mean age was 54.6 ± 11.3, and 46.8% of the patients were women. Women less frequently presented axial involvement (8% vs. 28%; p < 0.001) and more commonly had enthesitis (2 vs. 0.3; p < 0.001). They also had higher DAPSA (16.4 vs. 13.4; p < 0.001) and PsAID12 scores (4.1 vs. 2.9; p < 0.001), worse HAQ results (0.8 vs. 0.5; p < 0.001), and greater FACIT-F scores (32.7 vs. 38.1; p < 0.001). As for the comorbid conditions, women presented a higher leptin/BMI ratio (0.8 vs. 0.2; p < 0.001), higher levels of HADS-A (6.9 vs. 4.7; p < 0.001) and HADS-D (4.9 vs. 3.4; p < 0.001), and poorer ISI (9.3 vs. 7.0; p < 0.001). By sex, pain affecting women was associated with the leptin/BMI ratio (ß: 0.29; p < 0.004; 95%CI: 0.3-1.6) and sleep quality (ß: 0.31; p < 0.004; 95%CI: 0.04-0.25; R2: 0.26). The leptin/BMI ratio was not associated with pain in men (p = 0.46). Conclusions: Sex was associated with several clinical manifestations. Leptin/BMI ratio levels were associated with pain in women, but not in men.

Influence of comorbidities not associated with fibromyalgia on neuropathic pain in patients with psoriatic arthritis: relationship with clinical parameters.

Objective: Neuropathic pain (NP) may influence disease activity assessment in patients with psoriatic arthritis, this relationship being traditionally based on the presence of concomitant fibromyalgia. We analyzed the influence of other comorbidities on NP and the relationship between pain and various clinical parameters. Methods: A cross-sectional study was conducted in patients diagnosed with psoriatic arthritis, excluding patients with a previous diagnosis of fibromyalgia, depression, anxiety, diabetes and/or dyslipidemia under treatment. NP was identified using the painDETECT questionnaire (score > 18). Obesity and related clinical parameters, anxious and depressive symptoms, sleep quality and fatigue were assessed as comorbidities. Disease activity was measured using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) in peripheral involvement, the ASDAS-PCR in axial involvement, functioning and disease impact were measured using the Health Assessment Questionnaire-Disability Index and 12-item Psoriatic Arthritis Impact of Disease questionnaire, respectively. Results: Overall, 246 patients were included (136 men; 55%). The mean age was 53.4 ± 11.0 years. Forty-two patients had NP (17.1%). Patients with NP had higher leptin levels (OR: 1.03, 95% CI: 1.007-1.056; p < 0.01) and poor sleep quality (OR: 1.20, 95% CI: 1.09-1.297; p < 0.001). Patients with NP also had greater fatigue NRS (6.2 ± 2.2 vs. 2.4 ± 0.19, p < 0.001). Patients with NP had higher cDAPSA score (17.3 ± 5.4 vs. 8.9 ± 6.5, p < 0.001), poorer functioning (1.1 ± 0.5 vs. 0.4 ± 0.5, p < 0.001) and greater disease impact (6.1 ± 1.7 vs. 2.6 ± 1.9, p < 0.001). Conclusion: NP was correlated with sleep quality and serum leptin and may be associated with worse disease activity, functioning and disease impact.

Bioavailability of flumequine and diclofenac in mice exposed to a metal-drug chemical cocktail. Evaluation of the protective role of selenium.

BACKGROUND AND PURPOSE: Organisms, including humans, are subjected to the simultaneous action of a wide variety of pollutants, the effects of which should not be considered in isolation, as many synergies and antagonisms have been found between many of them. Therefore, this work proposes an in vivo study to evaluate the effect of certain metal contaminants on the bioavailability and metabolism of pharmacologically active compounds. Because the most frequent entry vector is through ingestion, the influence of the gut microbiota and the possible protective effects of selenium has been additionally evaluated. EXPERIMENTAL APPROACH: A controlled exposure experiment in mammals (Mus musculus) to a "chemical cocktail" consisting of metals and pharmaceuticals (diclofenac and flumequine). The presence of selenium has also been evaluated as an antagonist. Mouse plasma samples were measured by UPLC-QTOF. A targeted search of 48 metabolites was also performed. KEY RESULTS: Metals significantly affected the FMQ plasma levels when the gut microbiota was depleted. Hydroxy FMQ decreased if metals were present. Selenium minimized this decrease. The 3-hydroxy DCF metabolite was not found in any case. Changes in some metabolic pathways are discussed. CONCLUSIONS AND IMPLICATIONS: The presence of metals in the mouse diet as well as the prior treatment of mice with an antibiotic mixture (Abxs), which deplete the gut microbiota, has a decisive effect on the bioavailability and metabolism of the tested pharmaceuticals and dietary selenium minimize some of their effects.

Investigating the Alcohol Effects on the Response to Strenuous Exercise Training: Protocol for a Multidisciplinary Intervention Study in Young Healthy Adults-The BEER-HIIT Study.

High-intensity interval training (HIIT) is a time-efficient strategy to improve fitness and performance. Whereas the multiple and negative effects of high intake of alcohol have been widely studied, the effect of moderate alcohol doses after exercise is not clear, and it is currently under debate. For that, a total of 80 young healthy adults are studied and allocated into 5 groups, each including 16 participants. Four groups follow a HIIT program, while the fifth group is a control non-training group. The training groups will be randomized according to the characteristics of the ingested beverage (alcohol beer, beer 0.0%, sparkling water, or ethanol). The effects of HIIT on several aspects of physical performance and mental health in young healthy adults are evaluated, also the concomitant effect of daily and moderate alcohol consumption. The novelty of this study lies in the continuous measurement of the psychological parameters associated with carrying out a highly demanding training program in conjunction with alcohol consumption in moderate quantities, reflecting real-life conditions.