STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD. METHODS AND RESULTS: This was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131-3.136]), C-reactive protein (1.046 [1.020-1.073]), blood pressure >140/90 mmHg (2.686 [1.506-4.791]), fibrates (2.032 [1.160-3.562]), calcium channel blockers (2.082 [1.158-3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240-4.721]), heart failure (2.139 [1.032-4.433]), LDL-C >70 mg/dL (4.594 [1.401-15.069]), and diuretics (3.328 [1.677-6.605]) were associated with cardiovascular mortality. CONCLUSIONS: The composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.

Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study.

BACKGROUND AND OBJECTIVE: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. METHODS: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. RESULTS: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). CONCLUSION: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.

Making integration foundational in population health intervention research: why we need 'Work Package Zero'.

OBJECTIVES: We aimed to identify when and how integration should take place within evaluations of complex population health interventions (PHIs). STUDY DESIGN: Descriptive analytical approach. METHODS: We draw on conceptual insights that emerged through (1) a working group on integration and (2) a diverse range of literature on case studies, small-n evaluations and mixed methods evaluation studies. RESULTS: We initially sought techniques to integrate analyses at the end of a complex PHI evaluation. However, this conceptualization of integration proved limiting. Instead, we found value in conceptualizing integration as a process that commences at the beginning of an evaluation and continues throughout. Many methods can be used for this type of integration, including process tracing, realist evaluation, congruence analysis, general elimination methodology/modus operandi, pattern matching and contribution analysis. Clearly signposting when integrative methods should commence within an evaluation should be of value to the PHI evaluation community, as well as to funders and related stakeholders. CONCLUSIONS: Rather than being a tool used at the end of an evaluation, we propose that integration is more usefully conceived as a process that commences at the start of an evaluation and continues throughout. To emphasize the importance of this timing, integration can be described as comprising 'Work Package Zero' within evaluations of complex PHIs.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Functional inhibitory control dynamics in impulse control disorders in Parkinson's disease.

BACKGROUND: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. METHODS: Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. RESULTS: PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. CONCLUSIONS: During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties. © 2019 International Parkinson and Movement Disorder Society.

[Monitoring of COVID-19 patients by telemedicine with telemonitoring]. / Telemedicina con telemonitorización en el seguimiento de pacientes con COVID-19.

AIM: To asses if telemedicine with telemonitoring is a clinically useful and secure tool in the tracking of patients with COVID-19. METHODS: A prospective observational study of patients with COVID-19 diagnosis by positive PCR considered high-risk tracked with telemedicine and telemonitoring was conducted in the sanitary area of Lugo between March 17th and April 17th, 2020. Two groups of patients were included: Outpatient Tracing from the beginning and after discharge. Every patient sent a daily clinical questionnaire with temperature and oxygen saturation 3 times a day. Proactive monitoring was done by getting in touch with every patient at least 11 a day. RESULTS: 313 patients (52.4% female) with a total average age of 60.9 (DE 15.9) years were included. Additionally, 2 patients refused to join the program. Since the beginning, 224 were traced outpatient and 89 after being discharged. Among the first category, 38 (16.90%) were referred to Emergency department on 43 occasions; 18 were hospitalized (8.03%), and 2 deceased. Neither deaths nor a matter of vital emergency occurred at home. When including patients after admissions monitoring was done in 304 cases. One patient re-entered (0.32%) to the hospital, and another one left the program (0.32%). The average time of monitoring was 11.64 (SD 3.58) days, and 224 (73.68%) patients were discharged during the 30 days of study. CONCLUSIONS: Our study suggests that telemedicine with home telemonitoring, used proactively, allows for monitoring high-risk patients with COVID-19 in a clinically useful and secure way.

Nigrostriatal dopamine transporter availability, and its metabolic and clinical correlates in Parkinson's disease patients with impulse control disorders.

PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.

IgE-Mediated Sensitization to Galactose-α-1,3- Galactose (α-Gal) in Urticaria and Anaphylaxis in Spain: Geographical Variations and Risk Factors.

BACKGROUND: The objectives of this study were to investigate the prevalence of sIgE to galactose-α-1,3-galactose (α-gal) in individuals with acute urticaria or anaphylaxis from different geographical areas of Spain and to evaluate the relevance of demographics and lifestyle as risk factors for this immune response. METHODS: Participants were recruited from allergy departments at 14 Spanish hospitals. Patients aged 18 years or older presenting with urticaria or anaphylaxis were enrolled into one of 2 arms: cases and controls. An interviewer-administered questionnaire collecting demographic data, lifestyle habits, and the presence of cofactors was obtained from each participant. sIgE to α-gal and total IgE were determined using ImmunoCAP. sIgE levels ≥0.35 kU/L were considered a positive result. RESULTS: The study population comprised 160 cases and 126 controls. The median age was 44 years. The overall prevalence of a positive result of sIgE to α-gal was 15.7%; this was higher in cases (26.3%) than in controls (2.4%). The sIgE anti-α-gal positivity rate ranged from 37.68% (rural) to 15.38% (semiurban), and 7.85% (urban). The rates of positivity were 46.32%, (Northern), 0.72% (Center), and 0% (Mediterranean). A positive result for sIgE to α-gal was associated with a history of tick bites, participation in outdoor activities, pet ownership, and ingestion of mammalian meats or innards before the onset of symptoms. Only alcohol consumption could be implicated as a cofactor. CONCLUSION: Sensitization to α-gal in patients with urticaria or anaphylaxis differs considerably between the 3 geographical areas studied and is related to tick bites.

Trends of maxillofacial trauma: An update from the prospective register of a multicenter study in emergency services of Chile.

BACKGROUND: Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. MATERIAL AND METHODS: descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. RESULTS: 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p <0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). CONCLUSIONS: the profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records.

Effect of repeated frying on the physical characteristics, the formation of acrylamide and oil uptake of tortilla chips subjected to pre-drying treatment.

Even though snacks such as tortilla chips are gaining popularity, the high intake of these products may cause problems related to their fat and acrylamide content. In consequence, this study is aimed at evaluating the effect of pre-fry drying on the absorption of oil, physicochemical characteristics and formation of acrylamide in corn tortilla chips fried in ten batches. Pre-drying was carried out at 40 °C, 50 °C and 60 °C and two air velocities (1.0 m/s2 year 1.5 m/s2). Frying conditions were selected from pre-tests where the physicochemical variables of frying oils (palm olein and avocado oil) were measured. Acrylamide content was measured by GC-MS analyses. The results revealed that the type of oil did not show a significant effect on the physicochemical variables studied. Pre-dried chips showed a decrease in the final oil content of 41-58% (depending on the type of oil used) when compared to two brands of commercial chips. All the detected acrylamide concentrations on the samples were below the detection limit (20 µg/kg). According to our results, avocado oil may also be an option for producing corn tortilla chips.

Persistent alteration in behavioural reactivity to a mild social stressor in rhesus monkeys repeatedly exposed to sevoflurane in infancy.

BACKGROUND: Socio-emotional development is the expression and management of emotions, which in non-human primates can be examined using responses toward increasing levels of threat. Damage to the limbic system alters socio-emotional development in primates. Thus, neuronal and glial cell loss caused by exposure to general anaesthesia early in infancy might also impact socio-emotional development. We recently reported that repeated sevoflurane exposure in the first month of life alters emotional behaviours at 6 months of age and impairs visual recognition memory after the first year of life in rhesus monkeys. The present study evaluated socio-emotional behaviour at 1 and 2 yr of age in those same monkeys to determine the persistence of altered emotional behaviour. METHODS: Rhesus monkeys of both sexes were exposed to sevoflurane anaesthesia three times for 4 h each time in the first 6 weeks of life. At 1 and 2 yr of age, they were tested on the human intruder task, a well-established mild acute social stressor. RESULTS: Monkeys exposed to sevoflurane as infants exhibited normal fear and hostile responses, but exaggerated self-directed (displacement) behaviours, a general indicator of stress and anxiety in non-human primates. CONCLUSIONS: Early repeated sevoflurane exposure in infant non-human primates results in an anxious phenotype that was first detected at 6 months, and persists for at least 2 yr of age. This is the first demonstration of such a prolonged impact of early anaesthesia exposure on emotional reactivity.

Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Visual recognition memory is impaired in rhesus monkeys repeatedly exposed to sevoflurane in infancy.

BACKGROUND: Experimental studies in animals have shown that exposure to general anaesthesia in infancy can cause loss of cells in the central nervous system and long-term impairments in neurocognitive function. Some human epidemiological studies have shown increased risk of learning disability after repeated anaesthesia exposure in early childhood. Thus, we investigated in a highly translational rhesus monkey model, whether repeated exposure in infancy to the inhalation anaesthetic sevoflurane is associated with impaired visual recognition memory during the first two yr of life. METHODS: Rhesus monkeys of both sexes were exposed to sevoflurane inhalation anaesthesia on approximately postnatal day 7 and then again 14 and 28 days later, for four h each time. Visual recognition memory was tested using the visual paired comparison task, which measures memory by assessing preference for looking at a new image over a previously-viewed image. Monkeys were tested at 6-10 months of age, again at 12-18 months of age, and again at 24-30 months of age. RESULTS: No memory impairment was detected at 6-10 months old, but significant impairment (reduced time looking at the novel image) was observed at 12-18 and 24-30 months old. CONCLUSIONS: Repeated exposure of infant rhesus monkeys to sevoflurane results in visual recognition memory impairment that emerges after the first yr of life. This is consistent with epidemiological studies that show increased risk of learning disability after repeated exposure to anaesthesia in infancy/early childhood. Moreover, these deficits may emerge at later developmental stages, even when memory performance is unaffected earlier in development.

Responsiveness of pituitary to galanin throughout the reproductive cycle of male European sea bass (Dicentrarchus labrax).

The neuropeptide galanin (Gal) is a putative factor regulating puberty onset and reproduction through its actions on the pituitary. The present study investigated the pituitary responsiveness to galanin and the patterns of galanin receptors (Galrs) expression throughout the reproductive cycle of two years old male European sea bass (Dicentrarchus labrax), an important aquaculture species. Quantitative analysis of pituitary and hypothalamus transcript expression of four galr subtypes revealed differential regulation according to the testicular developmental stage, with an overall decrease in expression from the immature stage to the mid-recrudescence stage. Incubation of pituitary cells with mammalian 1-29Gal peptide induced significant changes in cAMP concentration, with sensitivities that varied according to the testicular development stages. Furthermore 1-29Gal was able to stimulate both follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) release from pituitary cell suspensions. The magnitude of the effects and effective concentrations varied according to reproductive stage, with generalized induction of Fsh and Lh release in animals sampled in January (full spermiation). The differential expression of galrs in pituitary and hypothalamus across the reproductive season, together with the differential effects of Gal on gonadotropins release in vitro strongly suggests the involvement of the galaninergic system in the regulation the hypothalamus-pituitary-gonad axis of male sea bass. This is to our knowledge the first clear evidence for the involvement of galanin in the regulation of reproduction in non-mammalian vertebrates.

Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish European sea bass.

Kisspeptins are well known as mediators of the coordinated communication between the brain-pituitary axis and the gonads in many vertebrates. To test the hypothesis that gonadal steroids regulate kiss1 and kiss2 mRNA expression in European sea bass (a teleost fish), we examined the brains of gonad-intact (control) and castrated animals, as well as castrated males (GDX) and ovariectomized females (OVX) that received testosterone (T) and estradiol (E2) replacement, respectively, during recrudescence. In GDX males, low expression of kiss1 mRNA is observed by in situ hybridization in the caudal hypothalamus (CH) and the mediobasal hypothalamus (MBH), although hypothalamic changes in kiss1 mRNA levels were not statistically different among the groups, as revealed by real-time PCR. However, T strongly decreased kiss2 expression levels in the hypothalamus, which was documented in the MBH and the nucleus of the lateral recess (NRLd) in GDX T-treated sea bass males. Conversely, it appears that E2 evokes low kiss1 mRNA in the CH, while there were cells expressing kiss2 in the MBH and NRLd in these OVX females. These results demonstrate that kisspeptin neurons are presumably sensitive to the feedback actions of sex steroids in the sea bass, suggesting that the MBH represents a major site for sex steroid actions on kisspeptins in this species. Also, recent data provide evidence that both positive and negative actions occur in key factors involved in sea bass reproductive function, including changes in the expression of gnrh-1/gonadotropin, cyp19b, er and ar genes and sex steroid and gonadotropin plasma levels in this teleost fish.

Directional random laser source consisting of a HC-ARROW reservoir connected to channels for spectroscopic analysis in microfluidic devices.

Light sources are used in optofluidic devices for real-time system control and quantitative analysis of important process parameters. In this work, we present a random laser source using a hollow-core antiresonant reflecting optical waveguide (HC-ARROW) containing the gain media inside a reservoir to reduce dye bleaching, which is connected to microchannel waveguides to increase beam directionality. The device is pumped externally and emits a highly coherent and collimated laser beam.

Is Microarray Analysis Really Useful and Sufficient to Diagnose Nut Allergy in the Mediterranean Area?

BACKGROUND: Component-based diagnosis on multiplex platforms is widely used in food allergy but its clinical performance has not been evaluated in nut allergy. OBJECTIVE: To assess the diagnostic performance of a commercial protein microarray in the determination of specific IgE (sIgE) in peanut, hazelnut, and walnut allergy. METHODS: sIgE was measured in 36 peanut-allergic, 36 hazelnut-allergic, and 44 walnut-allergic patients by ISAC 112, and subsequently, sIgE against available components was determined by ImmunoCAP in patients with negative ISAC results. ImmunoCAP was also used to measure sIgE to Ara h 9, Cora 8, and Jug r 3 in a subgroup of lipid transfer protein (LTP)-sensitized nut-allergic patients (positive skin prick test to LTP-enriched extract). sIgE levels by ImmunoCAP were compared with ISAC ranges. RESULTS: Most peanut-, hazelnut-, and walnut-allergic patients were sensitized to the corresponding nut LTP (Ara h 9, 66.7%; Cor a 8, 80.5%; Jug r 3, 84% respectively). However, ISAC did not detect sIgE in 33.3% of peanut-allergic patients, 13.9% of hazelnut-allergic patients, or 13.6% of walnut-allergic patients. sIgE determination by ImmunoCAP detected sensitization to Ara h 9, Cor a 8, and Jug r 3 in, respectively, 61.5% of peanut-allergic patients, 60% of hazelnut-allergic patients, and 88.3% of walnut-allergic patients with negative ISAC results. In the subgroup of peach LTP-sensitized patients, Ara h 9 sIgE was detected in more cases by ImmunoCAP than by ISAC (94.4% vs 72.2%, P < .05). Similar rates of Cora 8 and Jug r 3 sensitization were detected by both techniques. CONCLUSIONS: The diagnostic performance of ISAC was adequate for hazelnut and walnut allergy but not for peanut allergy. sIgE sensitivity against Ara h 9 in ISAC needs to be improved.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.