IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

Predicting the body core temperature of recreational athletes at the end of a 10 km self-paced run under environmental heat stress.

NEW FINDINGS: What is the central question of this study? The aim was to identify the factors predicting the body core temperature of athletes at the end of a 10 km self-paced run in a hot environment. What is the main finding and its importance? Hyperthermia in athletes subjected to self-paced running depends on several factors, highlighting the integrated control of core temperature during exercise under environmental heat stress. Five of the seven variables that significantly predicted core temperature are not invasive and, therefore, practical for use outside the laboratory environment: heart rate, sweat rate, wet-bulb globe temperature, running speed and maximal oxygen consumption. ABSTRACT: Measurement of body core temperature (Tcore ) is paramount to determining the thermoregulatory strain of athletes. However, standard measurement procedures of Tcore are not practical for extended use outside the laboratory environment. Therefore, determining the factors that predict Tcore during a self-paced run is crucial for creating more effective strategies to minimize the heat-induced impairment of endurance performance and reduce the occurrence of exertional heatstroke. The aim of this study was to identify the factors predicting Tcore values attained at the end of a 10 km time trial (end-Tcore ) under environmental heat stress. Initially, we extracted data obtained from 75 recordings of recreationally trained men and women. Next, we ran hierarchical multiple linear regression analyses to understand the predictive power of the following variables: wet-bulb globe temperature, average running speed, initial Tcore , body mass, differences between Tcore and skin temperature (Tskin ), sweat rate, maximal oxygen uptake, heart rate and change in body mass. Our data indicated that Tcore increased continuously during exercise, attaining 39.6 ± 0.5°C (mean ± SD) after 53.9 ± 7.5 min of treadmill running. This end-Tcore value was primarily predicted by heart rate, sweat rate, differences between Tcore and Tskin , wet-bulb globe temperature, initial Tcore , running speed and maximal oxygen uptake, in this order of importance (ß power values corresponded to 0.462, -0.395, 0.393, 0.327, 0.277, 0.244 and 0.228, respectively). In conclusion, several factors predict Tcore in athletes subjected to self-paced running under environmental heat stress. Moreover, considering the conditions investigated, heart rate and sweat rate, two practical (non-invasive) variables, have the highest predictive power.

Heart rate variability, thyroid hormone concentration, and neuropsychological responses in Brazilian navy divers: a case report of diving in Antarctic freezing waters.

Open-water diving in a polar environment is a psychophysiological challenge to the human organism. We evaluated the effect of short-term diving (i.e., 10 min) in Antarctic waters on autonomic cardiac control, thyroid hormone concentration, body temperatures, mood, and neuropsychological responses (working memory and sleepiness). Data collection was carried out at baseline, before, and after diving in four individuals divided into the supporting (n=2) and diving (n=2) groups. In the latter group, autonomic cardiac control (by measuring heart rate variability) was also assessed during diving. Diving decreased thyroid-stimulating hormone (effect size = 1.6) and thyroxine (effect size = 2.1) concentrations; these responses were not observed for the supporting group. Diving also reduced both the parasympathetic (effect size = 2.6) and sympathetic activities to the heart (ES > 3.0). Besides, diving reduced auricular (effect size > 3.0), skin [i.e., hand (effect size = 1.2) and face (effect size = 1.5)] temperatures compared to pre-dive and reduced sleepiness state (effect size = 1.3) compared to basal, without changing performance in the working memory test. In conclusion, short-term diving in icy waters affects the hypothalamic-pituitary-thyroid axis, modulates autonomic cardiac control, and reduces body temperature, which seems to decrease sleepiness.

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Polyethylene glycol improves current methods for circulating extracellular vesicle-derived DNA isolation.

BACKGROUND: Extracellular vesicles (EVs) are small membrane-bound vesicles which play an important role in cell-to-cell communication. Their molecular cargo analysis is presented as a new source for biomarker detection, and it might provide an alternative to traditional solid biopsies. However, the most effective approach for EV isolation is not yet well established. RESULTS: Here, we study the efficiency of the most common EV isolation methods-ultracentrifugation, Polyethlyene glycol and two commercial kits, Exoquick® and PureExo®. We isolated circulating EVs from the bloodstream of healthy donors, characterized the size and yield of EVs and analyzed their protein profiles and concentration. Moreover, we have used for the first time Digital-PCR to identify and detect specific gDNA sequences, which has several implications for diagnostic and monitoring many types of diseases. CONCLUSIONS: Our findings present Polyethylene glycol precipitation as the most feasible and less cost-consuming EV isolation technique.

Vocal emotion processing deficits in HIV-infected individuals.

We aimed to explore the brain imaging correlates of vocal emotion processing in a group of HIV+ individuals and to compare the vocal emotion processing of HIV+ individuals with a group of healthy adults. We conducted multiple linear regressions to determine the cerebral correlates of a newly designed vocal emotion processing test in a sub-group of HIV+ individuals who completed the cerebral magnetic resonance scan (n = 36). Separately, we test whether the association between our test scores and each cerebral measure persisted regardless of the presence of neurocognitive impairment. We also calculated differences in average test scores between the total HIV+ group (n = 100) and a healthy adult group (n = 46). We found a positive association between the test scores and several brain area volumes: right frontal, temporal and parietal lobes, bilateral thalamus, and left hippocampus. We found a negative association between inflammatory markers in frontal white matter and the test scores. After controlling by neurocognitive impairment, several brain area volumes remained positively associated to the prosody test scores. Moreover, the whole HIV+ sample had significantly poorer test scores than healthy adults, but only in the subset of HIV+ individuals with neurocognitive impairment. For the first time, our results suggest that cerebral dysfunctions in particular brain areas involved in the processing of emotional auditory stimuli may occur in HIV+ individuals. These results highlight the need for broad characterization of the neuropsychological consequence of HIV brain damages.

Other radiological lesions of the Lower Urinary Tract in patients after isolated pelvic radiotherapy and combined with surgery. / Otras lesiones radiológicas del tracto urinario inferior (TUI) en pacientes sometidos a radioterapia pélvica en monoterapia y combinada con cirugía.

INTRODUCTION: The cystographic study of patients who have undergone radiotherapy (RT) and pelvic surgeries is uncommon in the literature, not described in patients without complications, and mostly related to urinary fistulae. OBJECTIVE: The study of the lower urinary tract (LUT) by cystography in these patients, with a description of some other types of radiation lesions. METHODS: 127 cystographies have been performed (88 men and 39 women) in consecutive patients undergoing radiotherapy (RT) (48 monotherapy and 79 cases combined with surgery), with a mean age of 69.6 years, and a mean time from radiation of 215 months (17 years). A General Electric X ray equipment has been used. We studied: behavior of the bladder neck at rest and during micturition, assessment of vesicoureteral reflux (VUR), bladder morphology (BM), urethral strictures (UE) and fistulas (F). RESULTS: We observed: Filling phase bladder neck incompetence (BNI) (37.8%), bladder smooth morphology (60.6%), coughing urinary incontinence (UI) (26.4%), basal cystocele (64.7%) and Valsalva cystocele (96.6%), a normal opening bladder neck (96,1%), reduction of the urethral diameter during voiding (41.3%), and vesicoureteral reflux (VUR) (13.2%). Five cases of filling BNI, were all related to prostate cancer (PC) (one of them with colon cancer as well). There were six cases of fistulae (4.14%), five of them women. Forty two patients (28.96%) had reduced urethral lumen, thirty five of them affecting the posterior urethra (83%), five (11.9%) the anterior and, finally, two cases of mixed lesion (5%). 95% were patients with PC without concurrent interventions (67%). Significant differences were found regarding the gender and the background of pelvic surgery. The filling BNI (p=0.007), the irregular bladder morphology (p=0.004) and the reduction of the urethral lumen (p<0.001) have been found to be more common in male patients, while the coughing UI was more common in women (p=0.007). The study shows that BNI (p=0.046), VUR (p=0.02) and the IU due to cough (p=0.03) were more frequent in operated patients, while reduced urethral lumen was less common (p<0.01). Patients with VUR present more time from radiotherapy, but not in other cystography variables. There was a relationship between RT and the BNI, stress urinary incontinence, anterior urethral stricture and VUR. The risk factor was increased by surgery. CONCLUSIONS: Bladder neck incompetence, stress UI, anterior urethral stricture and VUR have been related to radiotherapy. Surgery increased the risk factor in operated patients.

1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients.

MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

Association between polymorphisms in the thymidylate synthase gene and risk of breast cancer in a Mexican population.

Breast cancer (BC) is the leading cause of cancer-related deaths among women in Mexico. Two single-nucleotide polymorphisms (SNPs) in the thymidylate synthase (TS) gene, the 28-base pair (bp) tandem repeat in the TS 5'-untranslated enhanced region (TSER) and the 6-bp insertion/deletion in the TS 3'-untranslated region (TS 3'-UTR), increase the rate of misincorporation of uridylate into DNA and may lead to chromosomal damage. We examined the association between these polymorphisms and BC risk in Mexican women according to menopause status. Mexican patients with initial BC diagnosis (N = 230) and 145 individuals from a reference general population group (RGP) were included. For statistical analysis, the BC group was divided into pre- and post-menopause groups (PRE and POST groups, respectively). We analyzed both TS polymorphisms (TSER and TS 3'-UTR) using polymerase chain reaction. Finetti analysis was used to evaluate inter-and intra-group differences. The results showed a high frequency for the 3R and ins6 alleles in the BC, RGP, PRE, and POST groups. No significant differences were observed for the TS and TSER genotype and allele frequency distributions between groups. We found that the TSER and TS 3'-UTR SNPs are not associated with BC risk in Mexican patients.

Functional networks involved in spatial learning strategies in middle-aged rats.

Our aim was to assess the way that middle-aged rats solve spatial learning tasks that can be performed using different strategies. We assessed the brain networks involved in these spatial learning processes using Principal Component Analysis. Two tasks were performed in a complex context, a four-arm radial maze, in which each group must use either an allocentric or an egocentric strategy. Another task was performed in a simple T-maze in which rats must use an egocentric strategy. Brain metabolic activity was quantified to evaluate neural changes related to spatial learning in the described tasks. Our findings revealed that two functional networks are involved in spatial learning in aged rats. One of the networks, spatial processing, is composed of brain regions involved in the integration of sensory and motivational information. The other network, context-dependent processing, mainly involves the dorsal hippocampus and is related to the processing of contextual information from the environment. Both networks work together to solve spatial tasks in a complex spatial environment.

Double-headed amphiphile-based sponge droplets: synthesis, characterization and potential for the extraction of compounds over a wide polarity range.

Supramolecular solvents (SUPRASs) are gaining momentum in the multi-residue analysis of liquid samples thanks to the delimited hydrophilic and hydrophobic microenvironments in their nanostructures. In this work, SUPRASs with increased hydrophilicity were synthesized with the aim of enhancing the extractability of polar compounds. For this purpose, a double-headed amphiphile, 1,2-decanediol, was self-assembled in hydro-organic media in the presence and absence of sodium chloride. The SUPRASs formed, characterized by scanning electron microscopy, consisted of sponge droplets made up of a highly convoluted three-dimensional (3D) network of amphiphile. The network contained interconnected bilayers that were intersected by similarly interconnected aqueous channels with high and nearly constant water content (∼30%, w/w). Both the inherently open structure of the sponge morphology and the increased hydrophilic-hydrophobic balance of the amphiphile, provided highly hydrophilic microenvironments into the aggregates that rendered in increased recovery factors for 15 perfluorinated compounds (PFCs, C4-C18, log Pow values from 0.4 to 11.6) in natural waters. Extraction took 15 min without further clean-up or evaporation of extracts which were readily compatible with LC-MS/MS quantitation. Absolute recoveries for PFCs, at the level of a few ng L-1, were in the range 70-120%, except for perfluoropentanoic acid (40%) and perfluorobutane sulfonic acid (51%). Detection limits for PFCs in water were in the range 0.01-0.02 ng L-1, which allowed their determination in slightly polluted waters (0.07-2.33 ng L-1). This work proves that hydrophilicity in SUPRASs can be tailored through the amphiphile and the morphology of their aggregates, and that this characteristic improves compound extractability in multi-residue analysis.

Analysis of conventional and nonconventional forensic specimens in drug-facilitated sexual assault by liquid chromatography and tandem mass spectrometry.

The incidence of drug-facilitated sexual assault (DFSA) has dramatically increased in the last decades. Forensic analytical scientists continuously seek new methods and specimens to prove the incidence of intoxication for the judiciary system. Factors influencing sample selection include the ease of obtaining the samples and the window of detection of the drugs, among others. Both conventional (blood, urine) and non-conventional specimens (hair, nails, fluids) have been proposed as suitable in DFSA cases. Reported sample treatments include a variety of liquid-liquid and solid-phase extraction as well as dilute-and-shoot procedures and microextraction techniques. Regarding analysis, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has emerged as the preferred confirmatory technique, due to its sensitivity, selectivity, and wide-scope applicability. In this review, we critically discuss the most common specimens and sample treatments/analysis procedures (related to LC-MS/MS) that have been reported during the last ten years. As a final goal, we intend to provide a critical overview and suggest analytical recommendations for the establishment of suitable analytical strategies in DFSA cases.

Monitoring endoscopic postoperative recurrence in Crohn's disease after an ileocecal resection. Does capsule endoscopy have a role in the short and long term?

Background: Small bowel capsule endoscopy (SBCE) is a noninvasive method to detect endoscopic postoperative recurrence (POR) after an ileocolonic resection in Crohn's Disease (CD). Few studies have evaluated the role of SBCE in the early POR (= 12 months). Data for detection of late POR (>12 months) and evaluation of treatment response in previous POR is scarce. We aimed to assess the SBCE performance in the three scenarios (early-POR, late-POR, and previous-POR). Methods: Retrospective 11-year cohort study of SBCE procedures performed on CD patients with ileocolonic resection. Disease activity by Rutgeerts score (RS), correlation with biomarkers, and therapeutic changes were recorded. Results: We included 113 SBCE procedures (34 early-POR, 44 late-POR, and 35 previous-POR). 105 procedures (92.9%) were complete and 97 SBCE (85.5%) were conclusive with no differences between groups. Relevant POR (RS ≥i2) was more frequent in the early-POR group compared to late-POR (58.8% vs 27.3%, p=0.02). In the previous-POR, RS improved in 43.5% of procedures, worsened in 26%, and remained unchanged in 30.5%. Fecal calprotectin (FCP) value of 100µg/g displayed the best accuracy: sensitivity 53.8%, specificity 78.8%, positive predictive value 66.7% and negative predictive value 68.4%. SBCE guided therapeutic changes in 43 patients (38%). No adverse events occurred in our cohort. Conclusion: SBCE is a safe and effective method to assess POR in the early and late setting in clinical practice, and for the evaluation of treatment response to previous POR. FCP is an accurate surrogate marker of POR and 100µg/g value had the best overall accuracy.

Preseason Training Improves Perception of Fatigue and Recovery From a Futsal Training Session.

PURPOSE: To compare the posttraining recovery timeline of elite Brazilian futsal athletes before (Pre-PS) and after 10 weeks of the preseason (Post-PS) period of high-intensity technical-tactical training. METHODS: At the start (n = 13) and at the end of the preseason (n = 7), under-20 male futsal players undertook fitness testing for maximal aerobic power, the countermovement jump (CMJ), and the 10-m sprint with change of direction. Furthermore, at both Pre-PS and Post-PS, the players participated in a training session where performance and psychophysiological measures were recorded before, immediately, 3, 24, and 48 hours postsession. The measures included CMJ, 10-m sprint, creatine kinase, Total Quality Recovery Scale, and Brunel Mood Scale. Effect size (ES) analyses compared fitness and posttraining recovery values for each parameter at Pre-PS versus Post-PS. RESULTS: Only trivial ES (-0.02 to 0.11) was evident in maximal aerobic power, CMJ, and 10-m sprint at Post-PS compared with Pre-PS. For the timeline of recovery, only trivial and small ESs were evident for the 10-m sprint (-0.12 to 0.49), though CMJ recovery was improved at 3 hours (0.87) and 48 hours (1.27) at Post-PS and creatine kinase was lower at 48 hours (-1.33) at Post-PS. Perception of recovery was improved in Post-PS at 3 hours (1.50) and 24 hours postsession (0.92). Furthermore, perception of effort was lower immediately after the session (-0.29), fatigue was lower at 3 hours (-0.63), and vigor responses were improved in all postseason assessments (0.59 to 1.13). CONCLUSION: Despite minimal changes in fitness, preseason training attenuated players' perception of effort and fatigue and improved their recovery profile following a high-intensity technical-tactical training session.

A new sample treatment strategy based on simultaneous supramolecular solvent and dispersive solid-phase extraction for the determination of ionophore coccidiostats in all legislated foodstuffs.

A single-step sample treatment, for the simultaneous extraction and clean-up for the determination of ionophore coccidiostats in EU legislated foodstuffs, is here proposed. The treatment is based on the combination of: (i) a supramolecular solvent with restricted access properties (SUPRAS-RAM), spontaneously formed by the addition of hexanol, water and THF to the sample; and (ii) dispersive solid phase extraction (dSPE). The SUPRAS-RAM extract was directly compatible with LC-MS/MS and no further re-extraction, evaporation or cleanup procedures were necessary. SUPRAS-RAM efficiently extracted the ionophores (recoveries in milk, eggs, fat, liver, kidney, and chicken and beef muscle were in the range 71-112%) and removed proteins and carbohydrates, whereas dSPE removed fats and other lipophilic compounds. The method was validated following the European Commission Decision 2002/657/EC. Detection limits (0.004-0.07 µg kg-1) were far below the maximum residue limits (1-150 µg kg-1). Method analytical and operational characteristics were suitable for routine determination of ionophores.

The role of clean intermittent catheterization in the treatment for detrusor underactivity. / El cateterismo vesical intermitente en la insuficiencia contráctil del detrusor.

OBJECTIVE: To study the influence of clean intermittent catheterization (CIC) on the lower urinary tract function in patients with urinary retention (UR) due to detrusor underactivity (DU). MATERIAL AND METHODS: A longitudinal study was carried out on 49 patients (28 men, 21 women) of mean age 55years, who underwent CIC for UR secondary to DU. The mean CIC frequency was 3.15 times/day. Patients' clinical data were collected, and they underwent urodynamic study before and after CIC, with a mean interval of 4years. Fisher's exact test was used for the analysis of categorical variables and Student's t test for parametric variables. The level of significance was set at 0.05 for a two-tailed test. RESULTS: The second urodynamic study showed a significantly increased bladder compliance, the Bladder Outlet Obstruction Index (BOOI) and the Bladder Contractility Index (BCI) also increased but without reaching statistical significance. There was a significantly higher percentage of benign prostatic hyperplasia (BPH) and acontractile detrusor cases among the group of patients whose BCI improved after CIC, with significantly lower CIC time. CONCLUSIONS: CIC improved bladder compliance in the patients of our series. The BCI improved in BPH patients and in patients with acontractile detrusor.

Hormonal, autonomic cardiac and mood states changes during an Antarctic expedition: From ship travel to camping in Snow Island.

We evaluated the influence of an Antarctic expedition, consisting of 26-day ship travel followed by 24-day camping in the Antarctic field during the summer season, on hormonal responses, autonomic cardiac control, and mood states in individuals that live in tropical regions. Data collection was carried out in 10 individuals on the 2nd, 16th, and 26th days aboard the ship (characterized by exposure to low-luminosity and temperature-controlled environments) and on the 4th, 11th, and 23rd days of camping in the Antarctic field (prolonged exposure to natural luminosity and cold environments). Morning samples of saliva (to determine testosterone and cortisol concentrations) and blood [to determine thyroid-stimulating hormone (TSH) and thyroxine (T4) concentrations] were obtained. Next, resting heart rate variability (HRV) was recorded, and the volunteers answered a mood questionnaire. Samples of saliva for measurement of melatonin concentration were obtained at night. At the end of ship travel, blood TSH and salivary melatonin increased by 15.6% and 72.3%, respectively, whereas salivary cortisol reduced by 37.1% compared to initial values and T4 reduced by 12.2% compared to 16th day. These hormonal changes occurred alongside increased depression score and biphasic changes in HRV parameters; for example, the RMSSD, a parasympathetic-related parameter, initially decreased by 47.8% and then returned towards baseline values by the end of the ship travel. In contrast, during the camp period, blood TSH and T4 reduced by 26.5% and 34.1%, respectively, and salivary cortisol increased by 72.1%, without concomitant changes in melatonin and HRV. Also, tension score transiently reduced and then increased towards the pre-camp score by the end of the field period. Testosterone remained unaltered throughout the expedition. In conclusion, ship travel and camping in Antarctica induced distinct neuroendocrine changes, cardiac autonomic regulation, and mood states. These specific changes most likely resulted from exposure to different natural luminosity, degrees of confinement, and ambient temperature in these environments.

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells.

Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.

Halogen bonding for increasing efficiency in liquid-liquid microextraction: Application to the extraction of hexabromocyclododecane enantiomers in river water.

Halogen bonding (XB) was here proposed, for the first time, as a solubilization mechanism for increasing efficiency in the liquid-liquid microextraction of halogenated compounds. The approach was illustrated by the extraction of hexabromocyclododecane (HBCD) enantiomers in natural waters with a supramolecular solvent (SUPRAS) made up of inverted hexagonal aggregates of decanoic acid. The XB and dispersion interactions offered by the SUPRAS were able to extract the six HBCD enantiomers (i.e. (+)-α-, (-)-α- (+)-ß-, (-)-ß-, (+)-γ- and (-)-γ-) quantitatively (e.g. recoveries in the range 89-106%) and reach concentration factors as high as 720 without the need for solvent evaporation. HBCD enantiomers in the SUPRAS extract were directly analysed by chiral liquid chromatography coupled to tandem mass spectrometry (LCMS/MS). Quantitation limits of the method (0.09-0.9 ng L-1) were below the quality standard stablished by the European Union for HBCDs in inland surface water samples (1.6 ng L-1), and the precision, expressed as relative standard deviation (n = 6), was below 9% for all the HBCD enantiomers at concentrations within the range 50-500 ng L-1. The method was successfully applied to the enantioselective determination of HBCDs in the dissolved and the particle-bound fractions of river waters containing different concentration of suspended particles (10-57.8 mg L-1) that were spiked at two concentration levels (10 and 100 ng L-1). The results here obtained prove that XB is a valuable mechanism for the solubilisation of halogenated compounds that can effectively increase their recovery from liquid and solid samples.