Guam ALS-PDC is a distinct double-prion disorder featuring both tau and Aß prions.

The amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) of Guam is an endemic neurodegenerative disease that features widespread tau tangles, occasional α-synuclein Lewy bodies, and sparse ß-amyloid (Aß) plaques distributed in the central nervous system. Extensive studies of genetic or environmental factors have failed to identify a cause of ALS-PDC. Building on prior work describing the detection of tau and Aß prions in Alzheimer's disease (AD) and Down syndrome brains, we investigated ALS-PDC brain samples for the presence of prions. We obtained postmortem frozen brain tissue from 26 donors from Guam with ALS-PDC or no neurological impairment and 71 non-Guamanian donors with AD or no neurological impairment. We employed cellular bioassays to detect the prion conformers of tau, α-synuclein, and Aß proteins in brain extracts. In ALS-PDC brain samples, we detected high titers of tau and Aß prions, but we did not detect α-synuclein prions in either cohort. The specific activity of tau and Aß prions was increased in Guam ALS-PDC compared with sporadic AD. Applying partial least squares regression to all biochemical and prion infectivity measurements, we demonstrated that the ALS-PDC cohort has a unique molecular signature distinguishable from AD. Our findings argue that Guam ALS-PDC is a distinct double-prion disorder featuring both tau and Aß prions.

Patient-centered outcomes after surgical treatment of peri-implantitis: a prospective clinical study.

BACKGROUND: Peri-implantitis is an inflammatory process affecting soft and hard tissues surrounding dental implants, causing progressive marginal bone loss. Peri-implant surgery is the treatment of choice. However, evidence about its impact on patients' quality of life (QoL) is limited. This study aimed to assess pain and QoL in the first seven post-operative days and measure patient satisfaction at the end of this period. MATERIAL AND METHODS: A prospective cohort study was conducted in patients with peri-implantitis. Patients reported pain on a visual analogue scale (VAS) ranging from 0 to 100mm every day during the first week after surgery. They then completed the OHIP-14sp questionnaire. A descriptive and inferential data analysis was used to assess the effect of surgical approach (resective, regenerative or combined), gender and working status on pain, satisfaction and QoL. RESULTS: Forty-one patients (93,2%) completed the daily pain VAS; scores ranged from 0 to 95 mm. Gender, occupation, or type of surgery had no significant effect upon its evolution. The mean total OHIP-14sp score was 16.7 (range = 5 to 33), indicating low to moderate deterioration in perceived oral health. Postoperative OHRQoL was significantly higher in working patients (mean difference (MD): 3.94; P = 0.042), and with the regenerative (MD: 6.34; P = 0.044) or the combined approach (MD: 5.41; P = 0.027). CONCLUSIONS: Considering the limitations of this study, postoperative pain was mild to moderate and decreased after the third day. Surgical treatment of peri-implantitis has an impact on QoL, especially when augmentation procedures are involved. This impact is higher in working patients.

[Assessment of the patient safety culture in the ICU of a second level hospital at the end of the third COVID-19 wave]. / Valoración de la cultura de seguridad del paciente en la UCI de un hospital de segundo nivel al finalizar la tercera oleada de COVID-19.

Introduction: Current healthcare settings and ICUs especially are complex, highly technical, and multidisciplinary, with interactions between healthcare professionals and users, in which there may be errors at different levels. Our objective was to assess the perception of patient safety in our unit at the end of the third wave of the COVID pandemic, with the intention of conducting subsequent improvement actions. Methods: Observational, cross-sectional, and descriptive study. The perception of Safety Culture was estimated using the HSOPS questionnaire translated into Spanish. Some questions were posed in a positive sense, and others in a negative sense. The response was also rated as positive, negative, or neutral. Our findings were compared visually, not mathematically, with those found in the previous national study «Analysis of the culture on patient safety in the hospital setting of the Spanish National Health System¼ published in 2009. A subgroup analysis was performed according to professional group and seniority as a health worker. The Student's t, χ? and ANOVA tests were used. Results: Sixty-two professionals responded to the questionnaire, 73.90% of the total. The median time working in ICU 2 years (interquartile range 2-4.5 years). The rating for the degree of safety was 8.06 (SD 1.16). The majority (91.20%) had not reported any adverse event in the last year. A total of 30.90% had recently received patient safety training. The dimensions considered as weaknesses were 9 («Staffing¼, with 27.57% of positive responses) and 10 ("Support of the hospital management in safety", with 17.64% of positive responses). The dimensions considered as strengths were 3 («Expectation of actions by management / supervision of the service¼) with 85.29% of positive responses, and 5 («Teamwork¼) with 95.58% of positive responses. The Cronbach's alpha index values suggest that the questionnaire has adequate internal consistency. In general, our data are more positive than those collected in the 2011 national survey, although the 2 dimensions considered weaknesses were already considered such in the previous work. Conclusions: The perception of patient safety in the ICU of our hospital after the end of the third wave of the COVID pandemic is adequate, with a more positive rating than that of the national study on safety culture at the hospital level carried out in 2009. The constant quest for patient safety should prioritize activity in the 2 dimensions considered weaknesses: staffing, and support from hospital management in everything related to patient safety.

Successful pulp revascularization of an autotransplantated mature premolar with fragile fracture apicoectomy and plasma rich in growth factors: a 3-year follow-up.

AIM: This case report demonstrates a positive outcome of the adjuvant use of fragile fracture (FF), which is a technique used to harvest dental pulp stem cells (DPSCs), and platelet-rich plasma (PRP) in a mandibular premolar (tooth 44) with a completely formed root that was transplanted into a surgically created socket and which maintained pulp vitality and function. SUMMARY: After virtual surgical planning, a 3D tooth replica of tooth 44 was fabricated. A surgical socket was created in the position of tooth 14; then, tooth 44 was extracted and the root dentine was abraded using a turbine diamond bur 3 mm from the apex until a circular groove was prepared around the outer circumference of the root; and then, an FF was performed without damaging the pulp tissue. PRP was placed in the socket, after which the donor tooth was inserted in the recipient area. At 2 weeks post-treatment, orthodontic traction was applied. At 3-year follow-up, the tooth had adequate alignment and was asymptomatic. Response to pulp testing was positive, and the presence of pulp canal obliteration was observed as a sign of pulpal healing. KEY LEARNING POINTS: Autotransplantation is a good alternative for replacing missing teeth, with repair of tissues and pulp revascularization. Revascularization of an autotransplanted mature tooth using the fragile fracture technique and PRP scaffold is a feasible option and might have positive effects on the long-term outcome of the procedure. Including completely formed teeth as donors in autotransplantation, maintaining vitality and their functions is an option that warrants further study.

CARDIOVASCULAR RISK FACTORS IN ADOLESCENTS: ROLE OF INSULIN RESISTANCE AND OBESITY.

INTRODUCTION: Childhood obesity is a public health problem characterized by early insulin resistance (IR), inflammation, and oxidative stress. The presence of an uninterrupted low-grade inflammatory state impairs metabolic and cardiovascular health. The population is particularly susceptible to develop metabolic disorders related to increased body fat. METHODS: Eighty-three adolescents were recruited and grouped according to HOMA-IR and BMI in either with or without IR and obese or normal-weight respectively. Anthropometric, biochemical, immunological and hormonal variables were determined. Transverse Analytical Study. RESULTS: Obesity, dyslipidemia, IL-6, and C-reactive protein were significantly higher in the IR group than in the non-IR group. Obese adolescents showed increased insulin levels, HOMA-IR, inflammatory markers, and triglycerides; while having lower HDL-C, and adiponectin when compared to normal-weight adolescents. As expected, obesity-related anthropometric markers positively correlated with IR and inflammatory markers while negatively correlated with adiponectin levels. CONCLUSIONS: Early IR, subclinical inflammation, dyslipidemia, and hypoadiponectinemia characterize obesity in adolescents. These factors may increase the risk of future coronary heart disease (CHD) and diabetes mellitus development (DM) in early adulthood.

National survey on the indicators of quality in Bioethics of the SEMICYUC in the departments of Intensive Care Medicine in Spain. / Encuesta nacional sobre los indicadores de calidad en Bioética de la SEMICYUC, en los servicios de Medicina Intensiva en España.

INTRODUCTION: Multiple interventions are performed in critical patients admitted to Intensive Care Units (ICUs). This study explores the presence in the daily practice of ICUs of elements related to the 6 bioethics quality indicators of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units, and the participation of their members in the hospital ethics committees. MATERIALS AND METHODS: A multicenter observational study was carried out, using a survey exploring descriptive aspects of the ICUs, with 25 questions related to bioethics quality indicators, and assessing the participation of ICU members in the hospital ethics committees. The ICUs were classified by size (larger or smaller than 10 beds) and type of hospital (public/private-public concerted center, with/without teaching). RESULTS: The 68 analyzed surveys revealed: daily informing of the family (97%), carried out in the information room (82%); end-of-life care protocols (44%); life support limitation form (48.43%); and physical containment protocol (40%). Compliance with the informed consent process referred to different procedures is: tracheostomy (92%), vascular procedures (76%), and extrarenal clearance (25%). The presence of ICU members in the hospital ethics committee is currently frequent (69%). CONCLUSIONS: Information supplied to relatives is adequate, although there are ICUs without an information room. Compliance with the informed consent requirements of various procedures is insufficient. The participation of ICU members in the hospital ethics committees is frequent. The results obtained suggest a chance for improvement in the bioethical quality of the ICU.

Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients. / Recomendaciones para el tratamiento de los pacientes críticos de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC).

The standardization of the Intensive Care Medicine may improve the management of the adult critically ill patient. However, these strategies have not been widely applied in the Intensive Care Units (ICUs). The aim is to elaborate the recommendations for the standardization of the treatment of critical patients. A panel of experts from the thirteen working groups (WG) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) was selected and nominated by virtue of clinical expertise and/or scientific experience to carry out the recommendations. Available scientific literature in the management of adult critically ill patients from 2002 to 2016 was extracted. The clinical evidence was discussed and summarised by the experts in the course of a consensus finding of every WG and finally approved by the WGs after an extensive internal review process that was carried out between December 2015 and December 2016. A total of 65 recommendations were developed, of which 5 corresponded to each of the 13 WGs. These recommendations are based on the opinion of experts and scientific knowledge, and are intended as a guide for the intensivists in the management of critical patients.

Recurrent wheezing and asthma after bocavirus bronchiolitis.

BACKGROUND: Human bocavirus (HBoV) was recently discovered and identified as an important cause of respiratory infection in young children. However, the relationship between HBoV-bronchiolitis and the development of recurrent wheezing has not yet been established. OBJECTIVE: We designed this study in order to describe the mid-term outcome, regarding the development of recurrent wheezing and asthma of HBoV-bronchiolitis patients and to compare it with RSV-bronchiolitis infants. METHODS: We studied 80 children (10 with HBoV and 70 with RSV infection), currently aged ≥4 years and previously hospitalised during the seasons 2004-2009 due to acute bronchiolitis. Epidemiological and clinical data were collected through structured clinical interviews at the follow-up visit. Spirometry and skin prick tests to common food and inhaled allergens were performed. RESULTS: All HBoV-patients developed recurrent wheezing and half of them had asthma at age 5-7 years. Almost 30% required hospital admission for recurrent wheezing. Asthma (odds ratio (OR)=1.28) and current asthma (OR=2.18) were significantly more frequent in children with HBoV-bronchiolitis than in RSV-bronchiolitis. FEV1 values were 99.2±4.8 in HBoV-group vs. 103±11 in RSV-group, p: 0.09. No differences were found with respect to allergic rhinitis, atopic dermatitis, food allergy, proportion of positive prick tests, and family history of atopy or asthma. CONCLUSIONS: Severe HBoV-bronchiolitis in infancy was strongly associated with asthma at 5-7 years.

Hospital admission due to respiratory viral infections in moderate preterm, late preterm and term infants during their first year of life.

BACKGROUND: Respiratory viral infections are a major cause of hospitalisation in infants <1 year and might cause severe symptoms in preterm infants. Our aim was to analyse admissions due to respiratory infections in moderate, late and term infants, and to identify risk factors for hospitalisation in preterm versus term. METHODS: Prospective study in a cohort of moderate and late preterm, and term infants born between October/2011 and December/2012. Admissions due to respiratory infections during the first year of life were analysed and compared among moderate (32-33), late (34-36) and term infants. Sixteen respiratory viruses were detected by RT-PCR. Clinical data were collected. RESULTS: 30 (20.9%) out of 143 preterm infants required admission for respiratory infection, versus 129 (6.9%) of 1858 term infants born in the same period (p<0.0001, OR: 3.6 CI 2.0 to 5.0). Hospitalised children had a higher prevalence of hyaline membrane disease (HMD) at birth (p<0.001, OR: 7.7 CI: 2.121 to 27.954) and needed more mechanical ventilation (p<0.001, OR: 5.7 CI: 1.813 to 18.396). Virus was identified in 25/30 (83%) preterm babies, and in 110/129 (85%) term infants. The most frequent viruses in preterm infants were RSV (76%) rhinovirus (20%). Clinical and epidemiological characteristics among term and preterm infants were similar. CONCLUSIONS: The risk of respiratory admissions during the first year of life is up to 3.6 times higher in moderate and late preterm. Once admitted, clinical features of respiratory episodes requiring hospitalisation are similar among term and preterm infants. Hyaline membrane disease and mechanical ventilation were also risk factors for respiratory admissions.

Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis.

OBJECTIVE: The impact of endogenous immunoglobulin isotypes on the prognosis of patients with severe sepsis has not been sufficiently explored. The aim of this study was to evaluate the association between immunoglobulin levels in plasma and survival in patients with this condition. DESIGN AND PATIENTS: A prospective multicentre cohort study was conducted. A total of 172 adult patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock were recruited. Patients were classified based on deciles of immunoglobulin concentrations at diagnosis of sepsis. Categorical variables were created and tested for their association with survival during hospitalization in the ICU. RESULTS: Overall, 42 patients died in the ICU during the study. Kaplan-Meier analysis showed that immunoglobulin concentrations below 300 mg dL(-1) for IgG1, 35 mg dL(-1) for IgM and 150 mg dL(-1) for IgA were associated with shorter survival times. Multivariate regression analysis showed that IgG1 < 300 mg dL(-1) was a risk factor for mortality [odds ratio (OR) 2.50, 95% confidence interval (CI) 1.04-6.03; P = 0.042]. The combined presence of IgG1, IgM and IgA levels below the described thresholds had a synergistic impact on mortality risk (OR 5.27, 95% CI 1.41-19.69; P = 0.013). A similar effect was observed for combined low levels of IgG1 and IgA (OR 4.10, 95% CI 1.28-13.12; P = 0.018) and also of IgG1 and IgM (OR 3.10. 95% CI 1.13-8.49; P = 0.028). CONCLUSIONS: The combined presence of low levels of the endogenous immunoglobulins IgG1, IgM and IgA in plasma is associated with reduced survival in patients with severe sepsis or septic shock. Assessment of the concentrations of these immunoglobulins could improve the results of treatment with exogenous immunoglobulins in patients with sepsis.

[Microbiological diagnosis of intra-abdominal infections]. / Diagnóstico microbiológico de las infecciones intraabdominales.

Intra-abdominal infections represent a large and wide group of diseases which include intra- and retro-peritoneal infections. Some of them could be defined as uncomplicated, where the infectious process is limited to the organ or tissue of origin (appendicitis, diverticulitis, cholecystitis…). Complications occur when the infection spreads to the peritoneum, triggering localised peritonitis and abdominal abscesses. Most intra-abdominal infections are due to perforation or inflammation of the intestinal wall. The microorganisms that cause these infections come from the gastrointestinal flora, and therefore produce polymicrobial infections mixed with a predominance of anaerobic bacteria. Microbiological diagnosis is essential to determine the aetiology and the susceptibility of antimicrobial agents of the microorganism involved, especially in nosocomial infections or in community infections in predisposed patients due to increasing bacterial resistance to antimicrobial agents, multidrug resistance and fungal involvement. Despite the advances in microbiological diagnosis, in the case of intra-abdominal infections it still remains direct, being based on stains and cultures, the most notable progress is the introduction of mass spectrometry (MALDI-TOF) for the rapid identification of the pathogens involved. This review will provide recommendations on the collection, transport and microbiological processing of clinical specimens. Comments on the pathogenesis, clinical and microbiological diagnosis of peritonitis primary, secondary, tertiary and peritonitis (and other infections) associated with peritoneal dialysis, intra-abdominal abscesses (intraperitoneal, retroperitoneal and visceral), biliary tract infections, appendicitis and diverticulitis are also presented.

Potential for automatic detection of calving in beef cows grazing on rangelands from Global Navigate Satellite System collar data.

Dystocia is one of the main causes of calf death around calving. In addition, peripartum deaths may occur due to other factors, such as weather or predators, especially in the case of grazing animals. Precision Livestock Farming (PLF) tools aimed at the automatic detection of calving may be useful for farmers, allowing cow assistance in case of dystocia or checking the condition of the cow-calf pair after calving. Such PLF systems are commercially available for dairy cows, but these tools are not suitable for rangelands, mainly due to power and connectivity constraints. Thus, since most commercial PLF tools for rangelands are based on Global Navigate Satellite System (GNSS) technology, the objective of this study was to design and evaluate several indicators built from data gathered with GNSS collars to characterise their potential for the detection of calving on rangelands. Location data from 57 cows, 42 of which calved during the study, were curated and analysed following a standardised procedure. Several indicators were calculated using two different strategies. The first approach consisted of having indicators that could be computed using the data of a single GNSS collar (cow indicators). The second strategy involved the use of data from several animals (herd indicators), which requires more animals to be monitored, but may allow the characterisation of social behaviour. Several indicators, such as the length of the daily trajectory or the sinuosity of cow path, showed significant differences between the pre- and postpartum periods, but no clear differences between calving day and previous days. Herd indicators, such as the distance to herd centroid or to the nearest peer were superior in terms of the detection of calving day, as cows showed isolation behaviour from 24 hours before calving. Relative indicators, i.e., the value of cow or herd indicators for the calving cow in relation to the average value of the same indicators for its herdmates, provided additional information on cow behaviour. For instance, according to the relative indicator for the change in daily trajectory, pregnant cows had a differential exploratory behaviour up to 14 days before calving. In conclusion, data from commercial GNSS collars proved to be useful for the computation of several indicators related to the occurrence of calving on rangelands. Some of those indicators showed changes from baseline values on the day before calving, which could serve to predict the onset of parturition.

[Reliability of MALDI-TOF mass spectrometry in the identification of anaerobic bacteria]. / Eficacia de la espectrometría de masas MALDI-TOF en la identificación de bacterias anaerobias.

AIM OF THE STUDY: MALDI-TOF mass spectrometry (MS) is becoming a major resource in the Clinical Microbiology laboratory. Results on some groups of microorganisms are still controversial. We have studied the reliability of MALDI-TOF MS for the identification of anaerobic clinical isolates was studied compared to conventional biochemical methods, with rRNA 16S sequencing being used as a reference when discrepancies arose. MATERIAL AND METHODS: A total of 126 anaerobic bacteria clinical isolates were studied by using API20A kits (bioMérieux, Marcy l'Étoile, France) and MALDI-TOF MS (Autoflex II, Bruker Daltonics, Germany), and using the data library BioTyper 2.0 (Bruker Daltonics, Germany). When discrepancies arose, or MALDI-TOF MS was not able to identify any microorganism, rRNA 16S sequencing was used as the reference standard. RESULTS: The biochemical method and MALDI-TOF MS agreed in identifying 60.9% of isolates at species level, and 20.3% of isolates at genus level. Among the 48 discrepancies observed, rRNA 16S sequencing supported MALDI-TOF MS identification, at species level, in 32 isolates (66.7%), and in 8 isolates (16.7%) at genus level. rRNA 16S sequencing supported biochemical identification in only two isolates (4.2%) at species level, and in 26 isolates (54.2%) at genus level. The eight isolates for which MALDI-TOF MS did not manage to identify, or the identification obtained was rejected by sequencing, belonged to species that are still not added to the BioTyper II data library. CONCLUSIONS: Results obtained in this study show that, overall, MALDI-TOF MS identification of anaerobic bacteria is more reliable than identification obtained by conventional biochemical methods (24% more correct identifications at species level). The number of major errors (incorrect identification at the genus level) is also 2.5-times lower. Moreover, all the major errors obtained by MALDI-TOF MS were due to the absence of some species in the data library. Thus, when data libraries are more complete, reliability differences between both methods will probably be even higher.

Proposing a sustainable urban 3D model to minimize the potential risk associated with green infrastructure by applying engineering tools.

The goal of this study is to estimate the potential risk of exposure to urban green infrastructure by calculating and improving of AIROT index, adding meteorological factors as wind direction and updating the index to be more accurate for smaller urban green areas. To achieve this objective, BIM methodology has been applied by creating a 3D BIM model from the reality capture of a street with LiDAR. The BIM model contains the parametric data needed to apply AIROT index and it allows to map results in a graphic environmental sustainability study. The importance of location of green infrastructure is one of main conclusions obtained in order to minimize aerobiological risks in future new buildings or even in maintenance tasks of urban green infrastructure. A valuable result obtained from the developed methodology are walk simulations in the 3D model with the aim to identify high risk of potential exposure of urban green infrastructure with allergenic interest for allergic patients in order to supply health itineraries of pedestrians in a proposal of Smart City.

Assessment of the patient safety culture in the ICU of a second level hospital at the end of the third COVID-19 wave.

INTRODUCTION: Current healthcare settings and ICUs especially are complex, highly technical, and multidisciplinary, with interactions between healthcare professionals and users, in which there may be errors at different levels. Our objective was to assess the perception of patient safety in our unit at the end of the third wave of the COVID pandemic, with the intention of conducting subsequent improvement actions. METHODS: Observational, cross-sectional, and descriptive study. The perception of Safety Culture was estimated using the HSOPS questionnaire translated into Spanish. Some questions were posed in a positive sense, and others in a negative sense. The response was also rated as positive, negative, or neutral. Our findings were compared visually, not mathematically, with those found in the previous national study «Analysis of the culture on patient safety in the hospital setting of the Spanish National Health System¼ published in 2009. A subgroup analysis was performed according to professional group and seniority as a health worker. The Student's t, χ2 and ANOVA tests were used. RESULTS: Sixty-two professionals responded to the questionnaire, 73.90% of the total. The median time working in ICU 2 years (interquartile range 2-4.5 years). The rating for the degree of safety was 8.06 (SD 1.16). The majority (91.20%) had not reported any adverse event in the last year. A total of 30.90% had recently received patient safety training. The dimensions considered as weaknesses were 9 ("Staffing", with 27.57% of positive responses) and 10 ("Support of the hospital management in safety", with 17.64% of positive responses). The dimensions considered as strengths were 3 ("Expectation of actions by management/supervision of the service") with 85.29% of positive responses, and 5 ("Teamwork") with 95.58% of positive responses. The Cronbach's alpha index values suggest that the questionnaire has adequate internal consistency. In general, our data are more positive than those collected in the 2011 national survey, although the 2 dimensions considered weaknesses were already considered such in the previous work. CONCLUSIONS: The perception of patient safety in the ICU of our hospital after the end of the third wave of the COVID pandemic is adequate, with a more positive rating than that of the national study on safety culture at the hospital level carried out in 2009. The constant quest for patient safety should prioritize activity in the 2 dimensions considered weaknesses: staffing, and support from hospital management in everything related to patient safety.

COMT and ANKK1 gene-gene interaction modulates contextual updating of mental representations.

The differential expression of the dopamine transmitter through its prefrontostriatal pathway has been proposed to account for individual differences in the updating of higher order task representations. Here we examined the interaction between two polymorphic variations of genes involved in the regulation of prefrontal and striatal dopamine (catechol-O-methyltransferase-COMT and ANKK1) on the neural mechanisms of task-set switching. A task-cueing paradigm was employed to measure behavioral costs and a scalp-recorded specific brain potential (novelty-P3) associated to distinct context updating operations in the face of either sensory or task novelty. The interaction between the COMT and ANKK1 genes was evidenced by corresponding specific behavioral costs and novelty-P3 amplitude enhancements reflecting task-set updating mechanisms. This effect was found only in individuals combining genes that yielded a balance between dopamine concentrations and receptor densities. Individuals displaying a putative "unbalance" showed enhanced novelty-P3 responses to all sensory changes, indicative of a task-set updating to sensory cues in a task-context independent fashion. These results support the epistasis of COMT and ANKK1 phenotypes in the flexible control of contextual information in humans.