[Withdrawal and reintroduction of pharmacological treatment of epilepsy in paediatric patients. Our experience]. / Retirada y reintroducción del tratamiento farmacológico de la epilepsia en pacientes pediátricos. Nuestra experiencia.

INTRODUCTION: There are many variables to be considered in the withdrawal of treatment for epileptic seizures, which requires a risk-benefit assessment. PATIENTS AND METHODS: A retrospective study of patients in a neuropaediatric practice who required the reintroduction of treatment for epilepsy after its initial withdrawal, and who continue to receive anti-seizure drugs. RESULTS: Twenty-three of 57 children whose treatment was withdrawn are currently being administered the treatment as a monotherapy. Attempts at withdrawal were made with 17 patients, with a mean seizure-free period of 26 months; range: 8-47 months (excluding one patient who never stopped presenting seizures). Mean age at the time of the last known data: 16 years; range: 7-28 years. Average time until the first seizure after withdrawal: 12 months; range: 1-82 months. Seizures persist despite the current treatment administered in eight cases. Two or three attempts to withdraw treatment were made in six patients, with a mean seizure-free period of 28.6 months; range: 22-48 months. Mean age at the time of the last known data: 18.68 years; range: 13-37 years. Average time until the first seizure after withdrawal: 8.2 months; range: 1-30 months. They presented seizures after treatment four was reintroduced. 52% of the patients presented seizures while receiving the drug, which was discontinued. The treatment was withdrawn in cases meeting criteria for persistent seizures: three refractory epilepsies, five symptomatic focal epilepsies, four cases with intellectual disability, five adolescent-onset epilepsies, and failures in previous withdrawal in 23 cases and 30 attempts. CONCLUSION: The decision to withdraw treatment must be personalised, and consider the risk of relapse, taking into account efficacy and tolerability, and behaviour and neurodevelopment in particular.

TITLE: Retirada y reintroducción del tratamiento farmacológico de la epilepsia en pacientes pediátricos. Nuestra experiencia.Introducción. Existen muchas variables que se deben considerar en la retirada del tratamiento anticrisis epilépticas, que precisa una evaluación riesgo-beneficio. Pacientes y métodos. Estudio retrospectivo en pacientes de una consulta de neuropediatría que precisaron reintroducir el tratamiento de la epilepsia tras su retirada inicial y continúan con fármacos anticrisis epilépticas. Resultados. De 57 niños a quienes se les retiró el tratamiento, 23 lo llevan actualmente, todos en monoterapia. En 17 se realizó un intento de retirada, con tiempo medio previo sin crisis de 26 meses; rango: 8-47 meses (excluido uno que nunca dejó de presentarlas). Edad media en el momento de los últimos datos conocidos: 16 años; rango: 7-28 años. Tiempo medio hasta nueva crisis tras retirada: 12 meses; rango: 1-82 meses. En ocho casos persisten crisis pese al tratamiento actual. En seis se realizaron 2-3 intentos, con un tiempo medio previo sin crisis de 28,6 meses; rango: 22-48 meses. Edad media en el momento de los últimos datos conocidos: 18,68 años; rango: 13-37 años. Tiempo medio hasta nueva crisis tras retirada: 8,2 meses; rango: 1-30 meses. Presentaron crisis una vez reintroducido el tratamiento cuatro. Había presentado crisis recibiendo el fármaco que se suspendió, el 52%. Se retiró el tratamiento a casos con criterios de persistencia de crisis: tres epilepsias refractarias, cinco focales sintomáticas, cuatro con discapacidad intelectual, cinco epilepsias de inicio en la adolescencia, y en 23 casos y 30 intentos fallidos en la retirada previa. Conclusión. La decisión de retirada debe ser individualizada, conociendo el riesgo de recaída, atendiendo a la eficacia y la tolerabilidad, especialmente el comportamiento y el neurodesarrollo.

CLT for NESS of a reaction-diffusion model.

We study the scaling properties of the non-equilibrium stationary states (NESS) of a reaction-diffusion model. Under a suitable smallness condition, we show that the density of particles satisfies a law of large numbers with respect to the NESS, with an explicit rate of convergence, and we also show that at mesoscopic scales the NESS is well approximated by a local equilibrium (product) measure, in the total variation distance. In addition, in dimensions d ≤ 3 we show a central limit theorem for the density of particles under the NESS. The corresponding Gaussian limit can be represented as an independent sum of a white noise and a massive Gaussian free field, and in particular it presents macroscopic correlations.

Stokes vector characterization by strongly measuring weak values.

We report the implementation of a non-standard procedure to perform Stokes polarimetry, which was recently proposed by considering weak value measurements. Our procedure is not restricted to weak measurements but applies for both weak and strong couplings between the observable being measured; the polarization (spin) vector; and the measuring device, the "pointer." In optics, the polarization-pointer coupling is usually implemented with a birefringent crystal. This applies in the weak coupling regime. We overcame this limitation by using an alternative setup in which one can go from weak to strong couplings by tuning a moveable mirror. We carried out our proof-of-concept experiments with a laser beam, the image of which was recorded and processed on a charge-coupled device. Our results illustrate that some concepts, originally introduced in a quantum context, in fact refer to properties that are common to both quantum and classical phenomena.

A Predictive and an Optimization Mathematical Model for Device Design in Cardiac Pulsed Field Ablation Using Design of Experiments.

Cardiac catheter ablation (CCA) is a common method used to correct cardiac arrhythmia. Pulsed Field Ablation (PFA) is a recently-adapted CCA technology whose ablation is dependent on electrode and waveform parameters (factors). In this work, the use of the Design of Experiments (DoE) methodology is investigated for the design and optimization of a PFA device. The effects of the four factors (input voltage, electrode spacing, electrode width, and on-time) and their interactions are analyzed. An empirical model is formed to predict and optimize the ablation size responses. Based on the ranges tested, the significant factors were the input voltage, the electrode spacing, and the on time, which is in line with the literature. Two-factor interactions were found to be significant and need to be considered in the model. The resulting empirical model was found to predict ablation sizes with less than 2.1% error in the measured area and was used for optimization. The findings and the strong predictive model developed highlight that the DoE approach can be used to help determine PFA device design, to optimize for certain ablation zone sizes, and to help inform device design to tackle specific cardiac arrhythmias.

In Vitro Models for Improved Therapeutic Interventions in Atrial Fibrillation.

Atrial fibrillation is the most common type of cardiac arrhythmias in humans, mostly caused by hyper excitation of specific areas in the atrium resulting in dyssynchronous atrial contractions, leading to severe consequences such as heart failure and stroke. Current therapeutics aim to target this condition through both pharmacological and non-pharmacological approaches. To test and validate any of these treatments, an appropriate preclinical model must be carefully chosen to refine and optimise the therapy features to correctly reverse this condition. A broad range of preclinical models have been developed over the years, with specific features and advantages to closely mimic the pathophysiology of atrial fibrillation. In this review, currently available models are described, from traditional animal models and in vitro cell cultures to state-of-the-art organoids and organs-on-a-chip. The advantages, applications and limitations of each model are discussed, providing the information to select the appropriate model for each research application.

Wave-particle duality in tripartite systems.

Quantum objects, sometimes called quantons, often display a characteristic feature referred to as wave-particle duality (WPD). Lately, this and other quantum traits have been subjected to intensive research, mainly motivated by the development of quantum information science. As a consequence, the scopes of some concepts have been extended, and it has been realized that they are not in the exclusive domain of quantum physics. This is particularly clear in optics, where qubits may show up as Jones vectors and WPD has its counterpart as wave-ray duality. WPD was originally addressed by focusing on a single qubit, which was afterwards supplemented with a second one playing the role of a path-marker in an interferometer setup. Fringe contrast, a sign of wave-like behavior, was proved to be diminished in connection with the effectiveness of the marker, the inducer of particle-like behavior. Going from bipartite to tripartite states is a natural and necessary step towards better understanding of WPD. This step is what we have accomplished in this work. We report some constraints ruling WPD for tripartite systems, as well as their experimental display with single photons.

Experimental display of generalized wave-particle duality.

The quantification of wave-particle duality (WPD) by means of measurable features associated to it, such as fringe visibility ($\mathcal {V}$) and path distinguishability ($\mathcal {D}$), led to the establishment of the constraint $\mathcal {V}^{2}+\mathcal {D}^{2} \leq \,1$. The two involved quantities refer to so-called "quantons", physical objects that are capable of generating an interferometric pattern, while being at least partially localizable. Any quanton's internal degree of freedom (DOF) can in principle be used as a path-marker. When the quanton and its internal DOF are simultaneously engaged, new constraints can be derived and experimentally tested. Generalized constraints show how $\mathcal {V}$ and $\mathcal {D}$ relate to other quantifiers and bring to light coherences that might remain otherwise hidden in both quantum and classical light. We submitted two-qubit constraints to experimental tests, using optical light beams. This shows that, despite the rather contrived nature of the constraints, linear optics setups are appropriate to test them. Our experimental results are in very good agreement with theoretical predictions related to the tested constraints. Our results also show that quantifiers such as $\mathcal {V}$ and $\mathcal {D}$ help not only to quantify, but also to generalize the concept of WPD.

Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro.

Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 µs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 µs and 5 µs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice.

[Oncogenetics]. / Oncogenetica.

Determining whether a hereditary cancer predisposition is present, is important for both the cancer patient and his family. It is relevant for surveillance and prevention or early detection of new tumours, treatment options and issues surrounding the desire to have children. For this reason, it must be ensured that for every patient with cancer (now or in the past) referral for genetic testing is considered. In this article we indicate how to take a family history and where to find and how to apply referral criteria if such a question arises in clinical practice. The consequences of a genetic diagnosis are illustrated by a breast cancer case.

α-synuclein pathogenesis in hiPSC models of Parkinson's disease.

α-synuclein is an increasingly prominent player in the pathology of a variety of neurodegenerative conditions. Parkinson's disease (PD) is a neurodegenerative disorder that affects mainly the dopaminergic (DA) neurons in the substantia nigra of the brain. Typical of PD pathology is the finding of protein aggregations termed 'Lewy bodies' in the brain regions affected. α-synuclein is implicated in many disease states including dementia with Lewy bodies (DLB) and Alzheimer's disease. However, PD is the most common synucleinopathy and continues to be a significant focus of PD research in terms of the α-synuclein Lewy body pathology. Mutations in several genes are associated with PD development including SNCA, which encodes α-synuclein. A variety of model systems have been employed to study α-synuclein physiology and pathophysiology in an attempt to relate more closely to PD pathology. These models include cellular and animal system exploring transgenic technologies, viral vector expression and knockdown approaches, and models to study the potential prion protein-like effects of α-synuclein. The current review focuses on human induced pluripotent stem cell (iPSC) models with a specific focus on mutations or multiplications of the SNCA gene. iPSCs are a rapidly evolving technology with huge promise in the study of normal physiology and disease modeling in vitro. The ability to maintain a patient's genetic background and replicate similar cell phenotypes make iPSCs a powerful tool in the study of neurological diseases. This review focuses on the current knowledge about α-synuclein physiological function as well as its role in PD pathogenesis based on human iPSC models.

Chromosome number variation in part of the flora of protected wild areas in the Araucania region of southern Chile / Variación del número cromosómico en parte de la flora de áreas silvestres protegidas en la región de la Araucanía, sur de Chile

ABSTRACT An analysis was made of the correspondence between species diversity and chromosome number (CN) diversity across 13 Protected Wild Areas (PWA) in the Araucanía Region of southern Chile, encompassing 84 plant species with available cytogenetic data. Our aim was to establish whether higher species diversity within a PWA entails higher CN variation as based on the index of chromosome number heterogeneity (ICNH). The CN data were extracted from databases for Chilean plants, and the ICNH for the flora of each PWA was calculated. Results showed that in nine PWA the species diversity clearly correlates with CN diversity. However, four PWA do not fit this trend. The percentage of species with CN data varied between 9.6% and 24.5% among PWA, with 11 PWA presenting percentages higher than 11%. A 27.3% of the Chilean vascular plant species with available cytogenetic data were studied here for the 13 PWA. The results obtained by studying one part of the flora with available CN data suggest that the PWA could be an important reservoir of genetic diversity at a chromosome level, thus justifying the protective role of the PWA as biodiversity conservation sites.

RESUMEN Se realizó un análisis de la correspondencia entre la diversidad de especies y la diversidad de números cromosómicos (CN) en 13 Áreas Silvestres Protegidas (PWA) en la Región de La Araucanía en el sur de Chile, incluyendo 84 especies de plantas con datos citogenéticos disponibles. El objetivo fue establecer si una mayor diversidad de especies dentro de un PWA implica una mayor diversidad en CN expresado en base al Índice de Heterogeneidad Cromosómica (ICNH). Los CN de cada especie se extrajeron de bases de datos para plantas chilenas y se calculó el ICNH para la flora de cada PWA. Los resultados mostraron que en nueve PWA la diversidad de especies se correlaciona claramente con la diversidad de CN. Sin embargo, cuatro PWA no se ajustan a esta tendencia. El porcentaje de especies con datos de CN varió entre 9,6% y 24,5% entre PWA, con 11 PWA presentando porcentajes superiores al 11%. Un 27,3% de las especies de plantas vasculares chilenas con datos citogenéticos disponibles fueron estudiadas para las 13 PWA. Los resultados obtenidos al estudiar parte de la flora sugieren que las PWA serían un reservorio importante de diversidad genética a nivel cromosómico como se muestra aquí, justificando así el papel protector de las PWA como sitios de conservación de la biodiversidad.

Comité de Ética Asistencial (CEA) del Hospital Regional de Talca, en pandemia COVID-19 / Care Ethics Committee (CEA) of Talca Regional Hospital, in COVID-19 pandemic

The healthcare ethics committee of the Regional Hospital of Talca, shares with the hospital community, ethical considerations in medical-clinical decisions, in the context of the COVID 19 pandemic. Focus attention on the person, with dignified treatment, with the center in quality and proportional to the individual condition, within the framework of protected teamwork, and that everyone is responsible for mutual care. The considerations of admission to critical units of complicated patients, with principles of caring over healing, without abandoning those who require assistance. Resources are scarce and must be protected, people must not be discriminated against, age is a precedent that must be considered, given the chances of survival, without going beyond the limitations to the therapeutic effort, which must be shared with the treating medical team and of the hospital ethics committee if required. A dignified death is an element to be considered with respect for the person, their families and the community.

Metastasis of colorectal carcinoma in the testis: first sign of peritoneal disease.

Metastases of colorectal carcinoma (CRC) in the testis are very rare and indicate an advanced stage of disease. In this case report, we present a patient with adenocarcinoma in the sigmoid colon with metastasis in the right testis. Testicular metastasis of CRC is mostly diagnosed late because of their low incidence rate. Patients with CRC and testicular metastasis have a poor prognosis. In this case, the patient turned out to have peritoneal metastasis and one should be aware that testicular metastasis could be the first sign of widespread disease.

Small Cell Carcinoma of the Esophagus: A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease.

BACKGROUND AND PURPOSE: Small cell carcinoma of the esophagus (SCEC) is a rare subtype of esophageal cancer for which optimal treatment is unknown. We analyzed the impact of treatment factors on outcome in patients with nonmetastasized SCEC. METHODS: Patients with a histologically confirmed SCEC without distant metastases were analyzed in a nationwide multicenter retrospective cohort. All patients received radiotherapy as part of curative treatment between January 2000 and December 2014. Details on treatment and outcome were retrieved from individual charts. Cox regression analysis was used to determine prognostic factors for survival. RESULTS: Fifty-eight patients were analyzed. Median survival was 16 months (95% confidence interval, 11-21 mo). Infield recurrences occurred in 25%, distant metastases in 45%, and brain metastases in 12%. In total, 63% of patients developed a recurrence. Most recurrences (67%) occurred within 1 year. In univariable analyses an increased number of chemotherapy cycles (>3) and lower radiotherapy doses (<45 Gy) were associated with improved survival. T-stage, N-stage, treatment period, type of chemotherapy, prophylactic cranial irradiation, and age were not associated with survival. In multivariable analyses, only the number of chemotherapy cycles was associated with better survival (hazard ratio, 0.78; P=0.006). CONCLUSIONS: SCEC recurs frequently at distant sites after definitive chemoradiotherapy and usually within 1 year after curative treatment. With a dose of 45 to 50 Gy, infield recurrence rate was low. We found a relationship between number of received chemotherapy cycles and survival with best results obtained after at least 4 cycles of chemotherapy.

Randomized clinical trial comparing liver resection with and without perioperative assessment of liver function.

BACKGROUND: Liver function tests may help to predict outcomes after liver surgery. The aim of this study was to evaluate the clinical impact on postoperative outcome and patient management of perioperative liver function testing using the LiMAx® test. METHODS: A multicentre RCT was conducted in six academic liver centres. Patients with intrahepatic tumours scheduled for open liver resection of at least one segment were eligible. Patients were randomized to undergo additional perioperative liver function tests (LiMAx® group) or standard care (control group). Patients in the intervention arm received two perioperative LiMAx® tests, one before the operation for surgical planning and another after surgery for postoperative management. The primary endpoint was the proportion of patients transferred directly to a general ward. Secondary endpoints were severe complications, length of hospital stay (LOS) and length of intermediate care/ICU (LOI) stay. RESULTS: Some 148 patients were randomized. Thirty-six of 58 patients (62 per cent) in the LiMAx® group were transferred directly to a general ward, compared with one of 60 (2 per cent) in the control group (P < 0·001). The rate of severe complications was significantly lower in the LiMAx® group (14 per cent versus 28 per cent in the control group; P = 0·022). LOS and LOI were significantly shorter in the LiMAx® group (LOS: 10·6 versus 13·3 days respectively, P = 0·012; LOI: 0·8 versus 3·0 days, P < 0·001). CONCLUSION: Perioperative use of the LiMAx® test improves postoperative management and reduces the incidence of severe complications after liver surgery. Registration number: NCT01785082 ( https://clinicaltrials.gov).

[Experience in an urban outpatient clinic with a mindfulness based intervention]. / Experiencia con intervención basada en mindfulness (atención plena) en pacientes de un centro de salud urbano.

AIM: In this study an evaluation is made of the effectiveness and acceptability of a mindfulness program oriented towards individuals in an outpatient clinic. The program attended to people had mild anxiety, stress, mild depression, chronic pain, or those with problems coping with their chronic disease condition. MATERIAL AND METHODS: The structured intervention was in 10 weekly 2 hour sessions. The study included 35 patients divided in two different groups. The variables associated with the different care qualities were measured using the five facet mindfulness questionnaire before the intervention and at two different times during the intervention: in the 5th week and at the end, in the 10th week. RESULTS: Statistically significant results were found with five facet mindfulness questionnaire questionnaire in the 5th week (10.52, p=.015) as well as in the 10th week (13.64, p=.039). According to acceptability, 47% of the patients came to 8 or more sessions, and no conflicts or disturbances were registered in relation to the organisation or the development of the program. CONCLUSION: Although these kinds of programs are effective and accepted in a Primary Care context, in future studies the clinical changes, and the impact on the health care system itself, should be analysed and measured.

Exploratory analysis for the identification of false banknotes using portable X-ray Fluorescence spectrometer.

The aim of this study was to verify if a portable X-ray fluorescence (pXRF) spectrometer can recognize the security features in banknotes that are reproducible by counterfeiters. Peruvian Nuevo Sol banknotes were studied: 4 genuine and 3 fake ones, in 11 points of analysis for each one, at all 77 data set. The correlation analysis of spectra among original notes was 1.0, and there was no correlation with fake banknotes. pXRF prove that two security features were reproducible for counterfeiters.

Probiotic Lactobacillus fermentum UCO-979C biofilm formation on AGS and Caco-2 cells and Helicobacter pylori inhibition.

The ability of the human isolate Lactobacillus fermentum UCO-979C to form biofilm and synthesize exopolysaccharide on abiotic and biotic models is described. These properties were compared with the well-known Lactobacillus casei Shirota to better understand their anti-Helicobacter pylori probiotic activities. The two strains of lactobacilli synthesized exopolysaccharide as detected by the Dubois method and formed biofilm on abiotic and biotic surfaces visualized by crystal violet staining and scanning electron microscopy. Concomitantly, these strains inhibited H. pylori urease activity by up to 80.4% (strain UCO-979C) and 66.8% (strain Shirota) in gastric adenocarcinoma (AGS) cells, but the two species showed equal levels of inhibition (~84%) in colorectal adenocarcinoma (Caco-2) cells. The results suggest that L. fermentum UCO-979C has probiotic potential against H. pylori infections. However, further analyses are needed to explain the increased activity observed against the pathogen in AGS cells as compared to L. casei Shirota.

Safety and efficacy of the addition of simvastatin to panitumumab in previously treated KRAS mutant metastatic colorectal cancer patients.

Panitumumab has proven efficacy in patients with metastatic or locally advanced colorectal cancer patients, provided that they have no activating KRAS mutation in their tumour. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification of KRAS. We hypothesize that the activity of the RAS-induced pathway in patients with a KRAS mutation might be inhibited by simvastatin. This would theoretically result in increased sensitivity to panitumumab, potentially comparable with tumours with wild-type KRAS. A Simon two-stage design single-arm, phase II study was designed to test the safety and efficacy of the addition of simvastatin to panitumumab in colorectal cancer patients with a KRAS mutation after failing fluoropyrimidine-based, oxaliplatin-based and irinotecan-based therapy. The primary endpoint of this study was the proportion of patients alive and free from progression 11 weeks after the first administration of panitumumab, aiming for at least 40%, which is comparable with, although slightly lower than, that in KRAS wild-type patients in this setting. If this 40% was reached, then the study would continue into the second step up to 46 patients. Explorative correlative analysis for mutations in the KRAS and related pathways was carried out. One of 14 patients was free from progression at the primary endpoint time. The median progression-free survival was 8.4 weeks and the median overall survival status was 19.6 weeks. We conclude that the concept of mutant KRAS phenotype expression modulation with simvastatin was not applicable in the clinic.