Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells.

Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+ monocytes, CD16+ neutrophils, and naive CD4+ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.

Transition mechanism of the coverage-dependent polymorphism of self-assembled melamine nanostructures on Au(111).

Molecular self-assembled films have recently attracted increasing attention within the field of nanotechnology as they offer a route to obtain new materials. However, careful selection of the molecular precursors and substrates, as well as exhaustive control of the system evolution is required to obtain the best possible outcome. The three-fold rotational symmetry of melamine molecules and their capability to form hydrogen bonds make them suitable candidates to synthesize this type of self-assembled network. In this work, we have studied the polymorphism of melamine nanostructures on Au(111) at room temperature. We find two coverage-dependent phases: a honeycomb structure (α-phase) for submonolayer coverage and a close-packed structure (ß-phase) for full monolayer coverage. A combined scanning tunnel microscopy and density functional theory based-calculations study of the transition regime where both phases coexist allows describing the mechanism underlying this coverage driven phase transition in terms of the changes in the molecular lateral tension.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

Customized retarders based on waveplates.

Phase control is a critical parameter in polarization measurements. It is well known that a proper combination of wave plates allows to obtain achromatic phase shift, i.e., a constant retardation in certain spectral ranges. This paper is focused on a different, but more useful, goal, as it is to achieve customized variable retarders in broad spectral ranges. To do that, a merit function was used to measure the similarity between the overall phase shift of the wave plate combinations and the desired target. The control variables are the thicknesses and orientations of the wave plates. All possible combinations with four and five wave plates of quartz and MgF2 were analyzed, but our approach can be perfectly extended to deal with more wave plates. The result of an optimization process determines the thicknesses and orientations of the wave plates, which results in the closest retarder to the desired one. Numerical results show deviations below 10% between the target and the obtained retardation. These systems are of special interest in those fields and instruments in which polarization control plays a fundamental role.

Design and Test of a High-Performance Wireless Sensor Network for Irradiance Monitoring.

Cloud-induced photovoltaic variability can affect grid stability and power quality, especially in electricity systems with high penetration levels. The availability of irradiance field forecasts in the scale of seconds and meters is fundamental for an adequate control of photovoltaic systems in order to minimize their impact on distribution networks. Irradiance sensor networks have proved to be efficient tools for supporting these forecasts, but the costs of monitoring systems with the required specifications are economically justified only for large plants and research purposes. This study deals with the design and test of a wireless irradiance sensor network as an adaptable operational solution for photovoltaic systems capable of meeting the measurement specifications necessary for capturing the clouds passage. The network was based on WiFi, comprised 16 pyranometers, and proved to be stable at sampling periods up to 25 ms, providing detailed spatial representations of the irradiance field and its evolution. As a result, the developed network was capable of achieving comparable specifications to research wired irradiance monitoring network with the advantages in costs and flexibility of the wireless technology, thus constituting a valuable tool for supporting nowcasting systems for photovoltaic management and control.

Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH).

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

An On-Line Low-Cost Irradiance Monitoring Network with Sub-Second Sampling Adapted to Small-Scale PV Systems.

Very short-term solar forecasts are gaining interest for their application on real-time control of photovoltaic systems. These forecasts are intimately related to the cloud motion that produce variations of the irradiance field on scales of seconds and meters, thus particularly impacting in small photovoltaic systems. Very short-term forecast models must be supported by updated information of the local irradiance field, and solar sensor networks are positioning as the more direct way to obtain these data. The development of solar sensor networks adapted to small-scale systems as microgrids is subject to specific requirements: high updating frequency, high density of measurement points and low investment. This paper proposes a wireless sensor network able to provide snapshots of the irradiance field with an updating frequency of 2 Hz. The network comprised 16 motes regularly distributed over an area of 15 m × 15 m (4 motes × 4 motes, minimum intersensor distance of 5 m). The irradiance values were estimated from illuminance measurements acquired by lux-meters in the network motes. The estimated irradiances were validated with measurements of a secondary standard pyranometer obtaining a mean absolute error of 24.4 W/m 2 and a standard deviation of 36.1 W/m 2 . The network was able to capture the cloud motion and the main features of the irradiance field even with the reduced dimensions of the monitoring area. These results and the low-cost of the measurement devices indicate that this concept of solar sensor networks would be appropriate not only for photovoltaic plants in the range of MW, but also for smaller systems such as the ones installed in microgrids.

Anti-D Alloimmunization after RhD-Positive Platelet Transfusion in RhD-Negative Women under 55 Years Diagnosed with Acute Leukemia: Results of a Retrospective Study.

BACKGROUND: Anti-D alloimmunization can occur when platelets from RhD-positive donors are transfused to RhD-negative patients, due to red blood cell residues in the platelet concentrates. METHODS: Our objective was to analyze the anti-D alloimmunization rate in a selected group of women under 55 years of age diagnosed with acute leukemia over an 18-year period. We focused the analysis on RhD-negative patients who received RhD-positive platelet transfusions. RESULTS: From January 1998 to October 2016, 382 women under 55 years were diagnosed with acute leukemia. A total of 56 patients were RhD-negative, and 48 (85.7%) received RhD-positive platelets. The median number of platelet concentrates transfused per patient was 23, and 48% of all platelet transfusions were RhD-positive. The 48 RhD-negative patients received a total of 949 RhD-positive platelet concentrates. Two patients developed anti-D: a 36-year-old woman with M3 acute myeloblastic leukemia and a 52-year-old patient with a secondary acute myeloblastic leukemia. CONCLUSION: We conclude that there is a need for agreement in the transfusion guidelines on the recommendation of anti-D alloimmunization prophylaxis. We suggest a possible benefit in favor of anti-D prophylaxis in childbearing women with acute leukemia.

Assessment of late cardiomyopathy by magnetic resonance imaging in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and idarubicin.

Late cardiomyopathy CMP is regarded as a potential severe long-term complication after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We assess by MRI the incidence and severity of clinical and subclinical long-term CMP in a cohort of adult APL patients in first complete remission with PETHEMA trials. Adult patients diagnosed with APL in first complete remission lasting ≥2 years underwent anamnesis and physical examination and were asked to perform a cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart failure accompanied by symptoms or by left ventricle ejection fraction (LVEF) <45% by MRI with or without symptoms. Subclinical CMP was defined as the following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or more of LVEF ≤55%, left ventricle end-diastolic volume index ≥98 ml/m2, left ventricle end-systolic volume index ≥38 ml/m2, right ventricle end-diastolic volume index ≥106 ml/m2 and regional wall motion abnormalities. Of the 82 patients enrolled in the study, median cumulative dose of anthracyclines (doxorubicin equivalence) was 650 mg/m2, and median time from APL diagnosis to the study was 87 months (range, 24-195). Seven out of 57 patients with available MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP by chest X-ray and physical assessment. In summary, we found 12% of subclinical and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA protocols. Due to the low number of patients, we must interpret our results cautiously.

Design of superachromatic quarter-wave retarders in a broad spectral range.

A superachromatic quarter-wave retarder using an arbitrary number of waveplates in a broadband spectral range has been proposed. Their design is based on the optimization of a merit function, the achromatism degree (AcD), which represents a global behavior metric for the retardation. By means of this technique, the thickness and azimuth of each waveplate is determined. The achromatism degree is a measure of the distance between the overall retardation and a target retardation weighted by the spectrum of the incident light. We report on a particular case where all waveplates are made of quartz. As application examples, the design of a quarter-wave retarder using two, three, and four waveplates in the spectral ranges of 500-700 nm and 400-1000 nm was studied. The numerical results show that for these ranges, the best designs obtained present a maximum difference of 0.013° and 0.010° with respect to the target retardation, respectively. In addition, an analysis of their achromatic stability is presented. These results can be applied in the aerospace industry, spectroscopic ellipsometry, and spectrogoniometry, among others.

Self-imaging technique for beam collimation.

A simple collimation technique based on measuring the period of one self-image produced by a diffraction grating is proposed. Transversal displacement of the grating is not required, and then automatic single-frame processing can be performed. The self-image is acquired with a CMOS camera, and the period is computed using the variogram function. Analytical and experimental results are obtained, which show the simplicity and accuracy of the proposed technique.

Study on the Interaction of Polymeric Chemical Additives with Phase Change Materials in Air Lime Renders.

The interaction of microencapsulated phase change materials (PCMs) with polymeric chemical additives in an air lime binding matrix was studied. These polymer-based additives included an adhesion booster (derived from starch) and a superplasticizer (polycarboxylate ether). Two different PCMs with melting points of 18 °C and 24 °C were assayed. The microcapsules were composed of melamine, with paraffin-based PCM cores. Measurements of zeta potential, particle size distribution, adsorption isotherms, and viscosity analyses were performed to comprehend the behavior of the polymer-based additives within the air lime matrix and their compatibility with PCMs. Zeta potential experiments pointed to the absence of a strong interaction between the lime particles and the microcapsules of PCMs. At the alkaline pH of the lime mortar, the negative charge resulting from the deprotonation of the melamine shell of the microcapsules was shielded by cations, yielding high positive zeta potential values and stable dispersions of lime with PCMs. The polycarboxylate ether demonstrated the ability to counteract the increase in mixing water demand caused by the PCM addition in the lime matrix. The dispersing action of the superplasticizer on the lime particles was seen to exert a collateral dispersion of the PCMs. Conversely, despite the positive values of zeta potential, the addition of the starch-based additive resulted in the formation of large PCM-lime clumps. Air lime renders incorporating 5, 10, and 20% PCMs by weight with various dosages of these chemical additives were experimented with until the optimal formulation for the specific application of the mortars as renderings was achieved. This fine-tuned formulation effectively tackled issues commonly associated with the addition of PCMs to mortars, such as poor adhesion, crack formation, and reduced fluidity.

Emergence of cooperation in the one-shot Prisoner's dilemma through Discriminatory and Samaritan AIs.

As artificial intelligence (AI) systems are increasingly embedded in our lives, their presence leads to interactions that shape our behaviour, decision-making and social interactions. Existing theoretical research on the emergence and stability of cooperation, particularly in the context of social dilemmas, has primarily focused on human-to-human interactions, overlooking the unique dynamics triggered by the presence of AI. Resorting to methods from evolutionary game theory, we study how different forms of AI can influence cooperation in a population of human-like agents playing the one-shot Prisoner's dilemma game. We found that Samaritan AI agents who help everyone unconditionally, including defectors, can promote higher levels of cooperation in humans than Discriminatory AI that only helps those considered worthy/cooperative, especially in slow-moving societies where change based on payoff difference is moderate (small intensities of selection). Only in fast-moving societies (high intensities of selection), Discriminatory AIs promote higher levels of cooperation than Samaritan AIs. Furthermore, when it is possible to identify whether a co-player is a human or an AI, we found that cooperation is enhanced when human-like agents disregard AI performance. Our findings provide novel insights into the design and implementation of context-dependent AI systems for addressing social dilemmas.

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Trajectory of Urine Albumin-Creatinine Ratio in Patients with Acute Heart Failure.

INTRODUCTION: Albuminuria is prevalent in patients with chronic heart failure and is a risk factor for disease progression. However, its clinical meaning in acute heart failure remains elusive. This study analyzed the trajectory of urine albumin to creatinine ratio (UACR) between admission and discharge and its association with decongestion. METHODS: In this prospective observational study, 63 patients were enrolled. UACR, B-type natriuretic peptide (BNP), and clinical congestion score (CCS) were obtained at admission and discharge. We used linear mixed regression analysis to compare changes in the natural logarithm of UACR (logUACR) and its association with changes in markers of decongestion. Estimates were reported as least squares mean with their respective 95% CIs. RESULTS: The median age of the study population was 87 years, 68.5% were women, and 69.8% had a left ventricular ejection fraction >50%. LogUACR at discharge significantly decreased in the overall population compared to admission (Δ -0.47, 95% CI: -0.78 to -0.15, p value = 0.003). The magnitude of UACR drop at discharge was associated with changes in surrogate markers of decongestion. Patients who showed a greater reduction in BNP at discharge exhibited a greater reduction in UACR (p = 0.016). The same trend was also found with clinical decongestion, as assessed by changes in CCS, however, without achieving statistical significance (p = 0.171). UACR change at discharge was not associated with changes in serum creatinine (p value = 0.923). CONCLUSION: In elderly patients with AHF and volume overload, the level of UACR significantly decreased upon discharge compared to admission. This reduction in UACR was closely linked to decreases in BNP.

Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions. Methods: To address the need for efficient, rapid, and cost-effective detection of CRLF2 alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate. Results: The method successfully identified CRLF2 expression, P2RY8::CRLF2 fusions, and CRLF2 and JAK2 variants, achieving a 100% sensitivity and specificity. Application of this method across 61 samples revealed that 24.59% exhibited CRLF2 overexpression, predominantly driven by IGH::CRLF2 (73.33%). High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Discussion: Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.

Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético).

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer.

INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.

Episodes of loss of consciousness in a patient with a background of cerebral venous thrombosis.

Episodes of loss of consciousness are common, even in young, healthy people, and can sometimes represent a diagnostic challenge. The main diagnoses to consider are syncope and epileptic seizures, both of which may have similar symptomatology such as dizziness, loss of consciousness, falls, or "convulsive" phenomena. We present the case of a young male patient with a background of two venous thrombosis episodes (superior vena cava thrombosis and cerebral venous thrombosis), attributed to protein C and S deficiency and complicated by high intracranial pressure. A lumboperitoneal shunt was performed and anticoagulant therapy was initiated. He did not experience any medical problems until several years later, when he suddenly began to develop frequent, repetitive, transient episodes of dizziness, followed by loss of consciousness. Simultaneous video-EEG and ECG performed during these events showed a typical pattern normally observed during syncope. Due to the absence of changes in heart rate or blood pressure, and taking into account his medical history, intracranial hypertension was considered as a possible cause of cerebral hypoperfusion. Cerebral arteriography demonstrated chronic thrombosis of all the cerebral sinuses, and the lumbar puncture an intracranial pressure of 47 mm Hg. The lumboperitoneal shunt was replaced and the patient has since not presented with any episodes. The use of simultaneous video-EEG and ECG is a reliable and efficient approach to differentiate between syncope and seizure and in this case, was the key to finding the cause of these episodes. [Published with video sequences].

Pharmacological treatment for challenging behavior in adults with intellectual disability: Systematic review and meta-analysis.

INTRODUCTION: Few evidence on the use of antipsychotics in people with intellectual disabilities and challenging behaviors, generates the need to develop studies that contribute to collect, compare and synthesize the available information. The present systematic review and meta-analysis aims to determine the clinical efficacy of antipsychotic medication in reducing critical episodes in this population. METHODS: We searched Web of Science, Scopus, EBSCO, Embase, and PubMed for randomized controlled trials of antipsychotic medication versus placebo. Preliminarily yielded 1354 abstracts and citations; six studies with 274 subjects met the inclusion criteria of studies with experimental design, longitudinal type, with pre- and post-intervention measurements. RESULTS: There is evidence for the use of psychotropic drugs in the acute management of challenging behaviors in patients with intellectual disability (SMD=-0.85; 95% CI=-1.69 to -0.01; p=0.05). CONCLUSIONS: Our results coincide with the recommendations on the efficacy of the use of antipsychotics. Although our study provides evidence, the limited number of studies included in this research does not allow us to obtain totally conclusive results, although it can be considered as a guide for future studies.