Nucleophagy contributes to genome stability through degradation of type II topoisomerases A and B and nucleolar components.

The nuclear architecture of mammalian cells can be altered as a consequence of anomalous accumulation of nuclear proteins or genomic alterations. Most of the knowledge about nuclear dynamics comes from studies on cancerous cells. How normal healthy cells maintain genome stability, avoiding accumulation of nuclear damaged material, is less understood. Here, we describe that primary mouse embryonic fibroblasts develop a basal level of nuclear buds and micronuclei, which increase after etoposide-induced DNA double-stranded breaks. Both basal and induced nuclear buds and micronuclei colocalize with the autophagic proteins BECN1 and LC3B (also known as MAP1LC3B) and with acidic vesicles, suggesting their clearance by nucleophagy. Some of the nuclear alterations also contain autophagic proteins and type II DNA topoisomerases (TOP2A and TOP2B), or the nucleolar protein fibrillarin, implying they are also targets of nucleophagy. We propose that basal nucleophagy contributes to genome and nuclear stability, as well as in response to DNA damage.

Fetal programming and lactation: modulating gene expression in response to undernutrition during intrauterine life.

BACKGROUND: Adverse environmental conditions during intrauterine life, known as fetal programming, significantly contribute to the development of diseases in adulthood. Fetal programming induced by factors like maternal undernutrition leads to low birth weight and increases the risk of cardiometabolic diseases. METHODS: We studied a rat model of maternal undernutrition during gestation (MUN) to investigate gene expression changes in cardiac tissue using RNA-sequencing of day 0-1 litters. Moreover, we analyzed the impact of lactation at day 21, in MUN model and cross-fostering experiments, on cardiac structure and function assessed by transthoracic echocardiography, and gene expression changes though qPCR. RESULTS: Our analysis identified specific genes with altered expression in MUN rats at birth. Two of them, Agt and Pparg, stand out for being associated with cardiac hypertrophy and fibrosis. At the end of the lactation period, MUN males showed increased expression of Agt and decreased expression of Pparg, correlating with cardiac hypertrophy. Cross-fostering experiments revealed that lactation with control breastmilk mitigated these expression changes reducing cardiac hypertrophy in MUN males. CONCLUSIONS: Our findings highlight the interplay between fetal programming, gene expression, and cardiac hypertrophy suggesting that lactation period is a potential intervention window to mitigate the effects of fetal programming. IMPACT: Heart remodeling involves the alteration of several groups of genes and lactation period plays a key role in establishing gene expression modification caused by fetal programming. We could identify expression changes of relevant genes in cardiac tissue induced by undernutrition during fetal life. We expose the contribution of the lactation period in modulating the expression of Agt and Pparg, relevant genes associated with cardiac hypertrophy. This evidence reveal lactation as a crucial intervention window for preventing or countering fetal programming.

A manual synchronous low energy shock impedance as a predictor of successful defibrillation testing during subcutaneous ICD implantation.

BACKGROUND: Guidelines recommend defibrillation testing (DFT) during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. Implant position, patient characteristics and device factors, such as shock impedance, influence defibrillation success. To evaluate the shock impedance, a manual synchronous 10J shock (low energy synchronous shock [LESS]) can be delivered, without the need to induce ventricular fibrillation (VF). OBJECTIVE: To compare LESS and DFT impedance values and to evaluate the diagnostic accuracy of LESS impedance for predicting a successful DFT during S-ICD implantation. METHODS: Consecutive S-ICD implantations were included. Shock impedances were compared by paired t-tests. Univariate analysis was performed to investigate factors associated with successful DFT. A prediction model of successful DFT based on LESS impedance was assessed by logistic regression. Receiver operating characteristic (ROC) curve, area under the ROC curve and the Hosmer-Lemeshow tests were used to evaluate the accuracy of LESS impedance. RESULTS: Sixty patients were included (52 ± 14 years; 69% male). LESS and DFT impedance values were highly correlated (r2 = 0.97, p < .01). Patients with a failed first shock had higher body mass index (BMI) (30 ± 3 vs. 25.7 ± 4.3, p = .014), higher mean LESS (120 ± 35Ω vs. 86. ± 23Ω, p = .0013) and DFT impedance (122 ± 33Ω vs. 87 ± 24Ω, p = .0013). ROC analysis showed that LESS impedance had a good diagnostic performance in predicting a successful conversion test (AUC 84% [95% CI: 0.72-0.92]) with a cutoff value of <94Ω to identify a successful DFT (sensitivity 71%, specificity 73%). CONCLUSION: LESS impedance values without the need to induce VF can intraoperatively predict a successful DFT.

Intraoperative ultrasound and magnetic resonance comparative analysis in brain tumor surgery: a valuable tool to flatten ultrasound's learning curve.

BACKGROUND: Intraoperative ultrasound (IOUS) is a profitable tool for neurosurgical procedures' assistance, especially in neuro-oncology. It is a rapid, ergonomic and reproducible technique. However, its known handicap is a steep learning curve for neurosurgeons. Here, we describe an interesting postoperative analysis that provides extra feedback after surgery, accelerating the learning process. METHOD: We conducted a descriptive retrospective unicenter study including patients operated from intra-axial brain tumors using neuronavigation (Curve, Brainlab) and IOUS (BK-5000, BK medical) guidance. All patients had preoperative Magnetic Resonance Imaging (MRI) prior to tumor resection. During surgery, 3D neuronavigated IOUS studies (n3DUS) were obtained through craniotomy N13C5 transducer's integration to the neuronavigation system. At least two n3DUS studies were obtained: prior to tumor resection and at the resection conclusion. A postoperative MRI was performed within 48 h. MRI and n3DUS studies were posteriorly fused and analyzed with Elements (Brainlab) planning software, permitting two comparative analyses: preoperative MRI compared to pre-resection n3DUS and postoperative MRI to post-resection n3DUS. Cases with incomplete MRI or n3DUS studies were withdrawn from the study. RESULTS: From April 2022 to March 2024, 73 patients were operated assisted by IOUS. From them, 39 were included in the study. Analyses comparing preoperative MRI and pre-resection n3DUS showed great concordance of tumor volume (p < 0,001) between both modalities. Analysis comparing postoperative MRI and post-resection n3DUS also showed good concordance in residual tumor volume (RTV) in cases where gross total resection (GTR) was not achieved (p < 0,001). In two cases, RTV detected on MRI that was not detected intra-operatively with IOUS could be reviewed in detail to recheck its appearance. CONCLUSIONS: Post-operative comparative analyses between IOUS and MRI is a valuable tool for novel ultrasound users, as it enhances the amount of feedback provided by cases and could accelerate the learning process, flattening this technique's learning curve.

Toxicogenomics of the Freshwater Oligochaete, Tubifex tubifex (Annelida, Clitellata), in Acute Water-Only Exposure to Arsenic.

A toxicogenomic approach was used for toxicity evaluation of arsenic in the aquatic environment, and differential gene expression was investigated from 24 h and 96 h water-only acute toxicity tests with the aquatic oligochaete, Tubifex tubifex (Annelida, Clitellata). Several toxicological endpoints (survival and autotomy) of the oligochaete and tissue residues were measured, and dose-response modelling of gene expression data was studied. A reference transcriptome of the aquatic oligochaete, T. tubifex, was reconstructed for the first time, and genes related to cell stress response (Hsc70, Hsp10, Hsp60, and Hsp83), energy metabolism (COX1), oxidative stress (Cat, GSR, and MnSOD), and the genes involved in the homeostasis of organisms (CaM, RpS13, and UBE2) were identified and characterised. The potential use of the genes identified for risk assessment in freshwater ecosystems as early biomarkers of arsenic toxicity is discussed.

Silver-Free Gold-Catalyzed Heterocyclizations through Intermolecular H-Bonding Activation.

Modulable monosulfonyl squaramides have been shown to exert activation of gold(I) chloride complexes through H-bonding in an intermolecular way. Combinations of (PPh3)AuCl or IPrAuCl complexes and an optimal sulfonyl squaramide cocatalyst bearing two 3,5-bis(trifluoromethyl)phenyl groups efficiently catalyzed diverse heterocyclizations and a cyclopropanation reaction, avoiding in all cases undesired side reactions. Computational studies indicate that the Au-Cl bond breaks by transligation to the triple bond in a ternary complex formed by the actual AuCl···HBD catalyst and the substrate.

Multifunctional Switch Based on Spin-Labeled Gold Nanoparticles.

The fabrication of multifunctional switches is a fundamental step in the development of nanometer-scale molecular spintronic devices. The anchoring of active organic radicals on gold nanoparticles (AuNPs) surface is little studied and the realization of AuNPs-based switches remains extremely challenging. We report the first demonstration of a surface molecular switch based on AuNPs decorated with persistent perchlorotriphenylmethyl (PTM) radicals. The redox properties of PTM are exploited to fabricate electrochemical switches with optical and magnetic responses, showing high stability and reversibility. Electronic interaction between the radicals and the gold surface is investigated by UV-vis, showing a very broad absorption band in the near-infrared (NIR) region, which becomes more intense when PTMs are reduced to anionic phase. By using multiple experimental techniques, we demonstrate that this interaction is likely favored by the preferentially flat orientation of PTM ligands on the metallic NP surface, as confirmed by first-principles simulations.

Studies on the Regioselective Rearrangement of Azanorbornanic Aminyl Radicals into 2,8-Diazabicyclo[3.2.1]oct-2-ene Systems.

Aminyl radicals are nitrogen-centered radicals of interest in synthetic strategies involving C-N bond formation due to their high reactivity. These intermediate radicals are generated by the reaction of an organic azide with tributyltin hydride (Bu3SnH) in the presence of substoichiometric amounts of azobisisobutyronitrile (AIBN). In this work, we report the regioselective rearrangement of azanorbornanic ([2.2.1]azabicyclic) aminyl radicals into 2,8-diazabicyclo[3.2.1]oct-2-ene systems. With the aim to establish the structural requirements for this ring expansion, we have studied the effect of different bridgehead atoms of the [2.2.1]bicyclic system and the presence of an alkyl substituent at C4. Attempts to perform this ring expansion on a monocyclic analogue have been also explored to evaluate the influence of the bicyclic skeleton on the rearrangement. A detailed mechanistic proposal supported by computational studies is reported.

Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients.

BACKGROUND: The objectives of this study were to assess the association between serum caspase 1 levels and known clinical and radiological prognostic factors and determine whether caspase 1was a more powerful predictor of outcome after traumatic brain injury (TBI) than clinical indices alone, to determine the association between the serum levels of caspase 1 and the 6-month outcome, and to evaluate if there is any association between caspase 1 with clinical and radiological variables. METHODS: This prospective and observational study was conducted in a university hospital and included patients with TBI who required hospital admission. Serum samples were collected at hospital admission and 24 h after TBI. Caspase 1 levels were determined by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were obtained to test the potential of caspase 1 to predict mortality (Glasgow Outcome Scale Extended score of 1) and unfavorable outcome (Glasgow Outcome Scale Extended scores of 1-4). Multivariate logistic regression was used to assess the effect of serum caspase 1 levels, adjusted by known clinical and radiological prognostic indices, on the outcome. RESULTS: One hundred thirty-two patients and 33 healthy controls were included. We obtained 6-month outcome in 118 patients. On admission, the mean serum levels of caspase 1 were higher in patients with TBI compared with controls (157.9 vs. 108.5 pg/mL; p < 0.05) but not at 24 h after TBI. Serum caspase 1 levels on admission were higher in patients with unfavorable outcomes (189.5 vs. 144.1 pg/mL; p = 0.009). Similarly, serum caspase 1 levels on admission were higher in patients who died vs. patients who survived (213.6 vs. 146.8 pg/mL; p = 0.03). A logistic regression model showed that the serum caspase 1 level on admission was an independent predictor of 6-month unfavorable outcomes (odds ratio 1.05; 95% confidence interval 1-1.11; p = 0.05). Caspase 1 levels were higher in patients with severe TBI compared with those with moderate TBI, those with mild TBI, and healthy controls (p < 0.001). We did not find any correlation between caspase 1 and the radiological variables studied. CONCLUSIONS: In this cohort of patients with TBI, we show that serum caspase 1 protein levels on admission are an independent prognostic factor after TBI. Serum caspase 1 levels on admission are higher in patients who will present unfavorable outcomes 6 months after TBI. Caspase 1 levels on admission are associated with the injury severity determined by the Glasgow Coma Scale.

Maternal and perinatal outcomes in women ≥40 years undergoing induction of labor compared with women <35 years: Results from 4027 mothers.

AIM: Cesarean section is known to be increased with advanced maternal age in women undergoing induction of labor (IOL), but there is less information regarding other possible adverse maternal and fetal outcomes. METHODS: Retrospective cohort study of singleton, nulliparous, at-term women undergoing IOL between January 2007 and September 2020. Outcomes studied were: cesarean section, failed induction rate, fetal distress, post-partum hemorrhage, post-partum hysterectomy, and need of transfusion. Neonatal variables analyzed were: Apgar score, umbilical cord pH, need of admission to neonatal intensive care unit, and mortality. RESULTS: A total of 4027 women met the inclusion criteria; 1968 (48.9%) of mothers were <35 years, 1283 (31.9%) were 35-39 years, 658 (16.3%) were 40-44 years, and 118 (2.9%) were ≥45 years. Results showed a significantly increased incidence of c-section in women ≥35 years, with an OR 1.79 (95% CI 1.50-2.14) for women 40-44 years and OR 3.95 (95% CI 2.66-5.98) for women ≥45 years. The main indication for cesarean delivery was failed IOL, and this risk was also significantly increased in women ≥40 years. These differences remained significant after adjustment for confounding factors. No other adverse maternal or fetal outcomes showed an association with age. CONCLUSION: Maternal age ≥40 years was associated with an increased risk of c-section after IOL at term compared with younger women, mainly because of failed induction, but no association with other adverse maternal or neonatal outcomes were found in our population. Risks and benefits of IOL in older women should be individually evaluated and adequately discussed with mothers.

Developing As and Cu Tissue Residue Thresholds to Attain the Good Ecological Status of Rivers in Mining Areas.

The study was performed on residue-effects datasets from polluted and unpolluted sites in the Nalón River basin (northern Spain). The effects were measured in terms of alteration of field macroinvertebrate communities, and measured as ecological status scores, and number of families and abundance of Ephemeroptera, Plecoptera and Trichoptera (EPT). Non-linear regression models of the field-measured tissue residues in 10 taxa related to the ecological status of the macroinvertebrate communities were used to derive effective tissue residues (ERs). These were estimated for the good/moderate boundary defined by the ecological quality ratio (EQRs) score and for the 50% reduction of EQR and EPT metrics. As, Cu, Hg and Se ERs were calculated for several macroinvertebrate taxa with different feeding styles. The ER dataset allowed us to estimate As and Cu hazardous concentrations (HC), using species sensitivity distribution models, and were interpreted as community thresholds. Further studies for Hg and Se are needed to complete the database required for HC estimation. The reliability and differences of the several thresholds were tested in a risk assessment using a tissue-residue approach (TRA) conducted with field organisms from Cauxa Creek, a tributary from the same basin exposed to high levels of metals in the sediments due to gold mining activities. This risk assessment identified that As and Cu tissue residues satisfactorily explained the reduction in the ecological status of the macroinvertebrate assemblages. Our results indicate that TRA can help in setting future environmental quality standards for the protection of aquatic biota.

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling.

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT1 receptors and NADPH oxidase, and lower expression of AT2, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.

Pancreatic lipoma: diagnostic boom of a rare mesenchymal tumor.

Following the incidental finding of a tumor in a 58-year-old female, diagnosed as pancreatic lipoma, histologically confirmed by fine-needle aspiration biopsy (FNAB) with endoscopic ultrasound (EUS), we made a review in our center between 2018 and 2020, with 14 cases diagnosed of pancreatic lipoma by computarized tomography (CT) or magnetic resonance imaging (MRI).

Identification of trans-AT polyketide clusters in two marine bacteria reveals cryptic similarities between distinct symbiosis factors.

Glutarimide-containing polyketides are known as potent antitumoral and antimetastatic agents. The associated gene clusters have only been identified in a few Streptomyces producers and Burkholderia gladioli symbiont. The new glutarimide-family polyketides, denominated sesbanimides D, E and F along with the previously known sesbanimide A and C, were isolated from two marine alphaproteobacteria Stappia indica PHM037 and Labrenzia aggregata PHM038. Structures of the isolated compounds were elucidated based on 1D and 2D homo and heteronuclear NMR analyses and ESI-MS spectrometry. All compounds exhibited strong antitumor activity in lung, breast and colorectal cancer cell lines. Subsequent whole genome sequencing and genome mining revealed the presence of the trans-AT PKS gene cluster responsible for the sesbanimide biosynthesis, described as sbn cluster. Strikingly, the modular architecture of downstream mixed type PKS/NRPS, SbnQ, revealed high similarity to PedH in pederin and Lab13 in labrenzin gene clusters, although those clusters are responsible for the production of structurally completely different molecules. The unexpected presence of SbnQ homologues in unrelated polyketide gene clusters across phylogenetically distant bacteria, raises intriguing questions about the evolutionary relationship between glutarimide-like and pederin-like pathways, as well as the functionality of their synthetic products.

The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis.

BACKGROUND: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. METHODS: We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. MAIN OUTCOME MEASURES: Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. RESULTS: Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32-3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11-2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43-8.94, p <  0.001) was also observed in positive mothers. CONCLUSION: This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.

Why do bugs perish? Range size and local vulnerability traits as surrogates of Odonata extinction risk.

Despite claims of an insect decline worldwide, our understanding of extinction risk in insects is incomplete. Using bionomic data of all odonate (603 dragonflies and damselflies) North American species, we assessed (i) regional extinction risk and whether this is related to local extirpation; (ii) whether these two patterns are similar altitudinally and latitudinally; and (iii) the areas of conservation concern. We used geographic range size as a predictor of regional extinction risk and body size, thermal limits and habitat association as predictors of local extirpation. We found that (i) greater regional extinction risk is related to narrow thermal limits, lotic habitat use and large body size (this in damselflies but not dragonflies); (ii) southern species are more climate tolerant but with more limited geographic range size than northern species; and (iii) two priority areas for odonate conservation are the cold temperate to sub-boreal northeastern USA and the transversal neo-volcanic system. Our approach can be used to estimate insect extinction risk as it compensates for the lack of abundance data.

Male fetal sex is associated with low maternal plasma anti-inflammatory cytokine profile in the first trimester of healthy pregnancies.

Male fetal sex associates with higher rates of materno-fetal complications. Inflammation and inadequate vasoactive responses are mechanisms implicated in obstetric complications, and alterations in maternal plasma cytokine profile and nitric oxide (NO) metabolites are potential predictive biomarkers. We aimed to assess if these parameters are influenced by fetal sex. A prospective, observational study was carried out in 85 healthy pregnant women with singleton pregnancies in the first trimester of gestation. A blood sample was extracted at the tenth week of gestation. In plasma, we assessed: 1) cytokines (micro-array): pro-inflammatory (IL1α, IL1 ß, IL6, TNFα), anti-inflammatory (IL4, IL10, IL13), and chemoattractant (IL8, MCP1, IFNγ), and 2) NO metabolites (liquid chromatography-tandem mass spectrometry and Griess reaction): L-arginine, ADMA, SDMA, nitrates (NOx). Women with a male fetus (n = 50) exhibited, compared with those with a female (n = 35): higher IL1ß (OR = 1.09 with 95% CI: 0.97-1.28), and lower IL13 (OR = 0.93 with 95% CI: 0.87-0.99), and higher plasma NOx (OR = 1.14 with 95% CI: 1.03-1.31). Our data suggest that fetal sex influences maternal plasma cytokine profile and NO in early pregnancy. Women with a male fetus may have a worse capacity to counteract an inflammatory response. They may have better vasodilator capacity, but in the presence of an oxidative environment, a higher nitrosative damage may occur. These data reinforce the need to include sex as variable in predictive models.

Sex Differences in Placental Protein Expression and Efficiency in a Rat Model of Fetal Programming Induced by Maternal Undernutrition.

Fetal undernutrition programs cardiometabolic diseases, with higher susceptibility in males. The mechanisms implicated are not fully understood and may be related to sex differences in placental adaptation. To evaluate this hypothesis, we investigated placental oxidative balance, vascularization, glucocorticoid barrier, and fetal growth in rats exposed to 50% global nutrient restriction from gestation day 11 (MUN, n = 8) and controls (n = 8). At gestation day 20 (G20), we analyzed maternal, placental, and fetal weights; oxidative damage, antioxidants, corticosterone, and PlGF (placental growth factor, spectrophotometry); and VEGF (vascular endothelial growth factor), 11ß-HSD2, p22phox, XO, SOD1, SOD2, SOD3, catalase, and UCP2 expression (Western blot). Compared with controls, MUN dams exhibited lower weight and plasma proteins and higher corticosterone and catalase without oxidative damage. Control male fetuses were larger than female fetuses. MUN males had higher plasma corticosterone and were smaller than control males, but had similar weight than MUN females. MUN male placenta showed higher XO and lower 11ß-HSD2, VEGF, SOD2, catalase, UCP2, and feto-placental ratio than controls. MUN females had similar feto-placental ratio and plasma corticosterone than controls. Female placenta expressed lower XO, 11ß-HSD2, and SOD3; similar VEGF, SOD1, SOD2, and UCP2; and higher catalase than controls, being 11ß-HSD2 and VEGF higher compared to MUN males. Male placenta has worse adaptation to undernutrition with lower efficiency, associated with oxidative disbalance and reduced vascularization and glucocorticoid barrier. Glucocorticoids and low nutrients may both contribute to programming in MUN males.

Simultaneous analysis of natural pigments and E-141i in olive oils by liquid chromatography-tandem mass spectrometry.

This work describes the development of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of carotenoids (ß-carotene, lutein, ß-criptoxanthin, neoxanthin, violaxanthin) and chlorophylls, as well as their related compounds (chlorophyll A and B, pheophytin A and B and the banned dyes Cu-pyropheophytin A, Cu-pheophytin A and B) in olive oils. For this purpose, the feasibility of electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) for the ionization of these compounds was evaluated and compared. Tandem mass spectrometry (MS/MS) fragmentation was discussed for each family of compounds, and the most characteristic and abundant product ions were selected to propose a selective and sensitive UHPLC-MS/MS method. The best results were obtained using APCI and APPI, while ESI provided the worst signal-to-noise ratio (S/N) for all compounds. For the analysis of olive oils, a simple solid-phase extraction (SPE) with silica cartridges was applied before the determination by UHPLC-MS/MS (APCI and APPI) in multiple reaction monitoring (MRM) mode. Method quality parameters were stablished, and the results demonstrate the good performance of the new methods, providing low limits of detection (0.004-0.9 mg L-1), high extraction efficiencies (62-95%) and low matrix effects (< 25%). The developed UHPLC-API-MS/MS (APCI and APPI) methods were applied to the analysis of olive oil samples, and ß-carotene, pheophytin A, pheophytin B and lutein were detected and quantified in all of them at concentrations ranging from 0.1 to 9.5 mg L-1. Graphical abstract.

Growth prediction in asymptomatic meningiomas: the utility of the AIMSS score.

BACKGROUND: Management of asymptomatic meningiomas represents a challenge due to the absence of a solid consensus on which is the best management strategy. There are various known factors predicting meningiomas growth risk. However, the Asian Intracranial Meningioma Scoring System (AIMSS) is the only described score to quantify such risk thus emerging as a potential tool for management decisions. This study aims to validate this score on our series of asymptomatic meningiomas. METHOD: We performed a retrospective review of asymptomatic meningiomas diagnosed at our institution between January 2008 and October 2016 and followed by an annual cerebral Magnetic Resonance Imaging (MRI). For each lesion, the AIMSS score was calculated thus classifying them in low (0-2), intermediate (3-6) or high risk (7-11) of rapid growth (>2cm3/year). We investigated the correlation between the expected Average Growth Rate (AGR) according to the score and the one obtained in our study. The mean growth velocity over the different risk groups was also compared. RESULTS: Overall, 69 asymptomatic meningiomas found incidentally in 46 patients were included in the study; 31 were assigned to the low-risk group, 34 to the intermediate-risk group and 4 to the high-risk group. Attending to the AGR, 0% showed rapid growth in the low-risk group, 12% in the intermediate-risk group, and 25% in the high-risk group. The mean growth velocity showed a significant difference over the different risk groups (p < 0,001). CONCLUSIONS: According to our finding, the AIMSS score is a valid tool to estimate the risk of rapid growth of asymptomatic meningiomas. It is especially useful distinguishing between low- and intermediate-risk meningiomas. This feature would allow physicians to adjust the periodicity of radiological and clinical controls. Adding more known risk factors of rapid growth to the score might improve its predictive capabilities with the high-risk group.