Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.

BACKGROUND: Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB. METHODS: Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo. RESULTS: We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-mediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition. CONCLUSIONS: WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.

Dermatitis herpetiforme en mujer joven de la Amazonía peruana

La dermatitis herpetiforme es una enfermedad autoinmune que se caracteriza por la presencia de lesiones vesiculares y prurito en la superficie extensora de las extremidades, nalgas y parte baja de la espalda. Se presenta el caso clínico de una mujer de 21 años, natural y procedente de Iquitos, que presentó múltiples vesículas dolorosas, pruriginosas, de base eritematosa y purulentas en ambos codos durante un mes. Posteriormente, estas lesiones se diseminaron a ambas rodillas y se agregó prurito intenso. La paciente experimentó períodos alternantes de remisión y exacerbación. La correlación del cuadro clínico, resultados serológicos y de biopsia, junto con respuesta terapéutica a la dapsona confirmaron el diagnóstico de dermatitis herpetiforme, con una evolución favorable y remisión de la enfermedad.

Dermatitis herpetiforme is an autoimmune disease characterized by the presence of vesicular lesions and itching on the extensor surface of the limbs, buttocks, and lower back. The clinical case of a 21-year-old woman, a native of and from Iquitos, is presented. She presented multiple painful, itchy vesicles with an erythematous and purulent base on both elbows for a month. Subsequently, these lesions spread to both knees, and intense itching was added. The patient experienced alternating periods of remission and exacerbation. The correlation of the clinical picture, serological and biopsy results, along with the therapeutic response to dapsona, confirmed the diagnosis of dermatitis herpetiforme, with a favorable evolution and remission of the disease.

Validation of the aberrant salience inventory in a general and clinical Spanish population.

BACKGROUND: The concept of aberrant salience is related to the onset of psychosis. Its study is important for early identification and possible intervention in processes activating later positive symptoms. OBJECTIVES: This study validated the Spanish Aberrant Salience Inventory (ASI) for adult and clinical populations. METHODS: The sample consisted of 6178 participants, of whom 4523 were adolescents, 1292 were general population adults and 363 were patients with a psychopathology. RESULTS: The evidence provided validates the instrument's structure. Invariance of measurement suggests that both men and women, patients and nonclinical population (adults and adolescents) interpreted the items on the ASI similarly. The distribution of scores by age also suggests stabilization of the trend at about 19 years of age, showing a developmental change in motivational response. The hypothesis that patients, and in particular, those diagnosed with schizophrenia and other psychotic disorders and bipolar disorders would have the highest average scores in aberrant salience was met. CONCLUSIONS: This is a valuable instrument for evaluating a complex process related to abnormal motivation in the development of schizophrenia.

Collaborative Research Activities of the Arase and Van Allen Probes.

This paper presents the highlights of joint observations of the inner magnetosphere by the Arase spacecraft, the Van Allen Probes spacecraft, and ground-based experiments integrated into spacecraft programs. The concurrent operation of the two missions in 2017-2019 facilitated the separation of the spatial and temporal structures of dynamic phenomena occurring in the inner magnetosphere. Because the orbital inclination angle of Arase is larger than that of Van Allen Probes, Arase collected observations at higher L -shells up to L ∼ 10 . After March 2017, similar variations in plasma and waves were detected by Van Allen Probes and Arase. We describe plasma wave observations at longitudinally separated locations in space and geomagnetically-conjugate locations in space and on the ground. The results of instrument intercalibrations between the two missions are also presented. Arase continued its normal operation after the scientific operation of Van Allen Probes completed in October 2019. The combined Van Allen Probes (2012-2019) and Arase (2017-present) observations will cover a full solar cycle. This will be the first comprehensive long-term observation of the inner magnetosphere and radiation belts.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Social support, coping strategies and sociodemographic factors in women with breast cancer.

INTRODUCTION: The aim of this study was to analyze the associations between perceived social support and sociodemographic variables on coping strategies. METHODS: A prospective, cross-sectional, multicenter study was conducted in 404 women with resected, non-metastatic breast cancer. Participants completed questionnaires: perceived social support (MSPSS), coping strategies (Mini-MAC), and psychological distress (BSI-18). RESULTS: Sociodemographic factors as age, education, and partnership status were associated with coping strategies. As for maladaptive strategies, hopelessness was more frequent in older people and lower educational level; fatalism in older and single people, and cognitive avoidance was associated with lower educational level. Suppor t from family, friends, and partners was associated with a greater fighting spirit. In contrast, high psychological distress (anxiety and depression) was associated with greater use of maladaptive strategies. CONCLUSION: Young people, a high level of education, having a partner, low psychological distress, and seeking social support were associated with the use of adaptive cancer coping strategies.

[Current status of epilepsy surgery in Spain. Compendium and awareness]. / Estado actual de la cirugía de la epilepsia en España. Compendio y conciencia.

INTRODUCTION: Drug-resistant epilepsy affects between a third and a quarter of patients with epilepsy. Within this group, with a poorer quality of life and high healthcare costs, there is a considerable proportion of patients with potentially surgical causes of epilepsy, and epilepsy surgery is a proven therapeutic option. In Spain, we do not know the actual number of patients who are treated in relation to the total number of cases of refractory epilepsy that could benefit from surgical treatment. AIM: To analyse the number of epilepsy surgical interventions performed and published in relation to the potential cases of refractory epilepsy who are candidates for surgery in our country. METHOD: A review was carried out through a literature search in PubMed and Cochrane of articles published between 1990 and 2020, combining the following words and Boolean operators: 'epilepsy surgery IN Spain'. The evidence and recommendations were classified according to the prognostic criteria of the Oxford Centre for Evidence Based Medicine (2001) and of Neurological Societies (2004) for therapeutic actions. RESULTS: The majority (75.6%) of the publications came from the autonomous communities of Madrid and Catalonia and 46.4% of the articles published were short series. We counted 2,113 surgical interventions (resections, palliative interventions, implantation of deep electrodes and implantation of neurostimulators), which represents 8.7% of the estimated population with refractory epilepsy. CONCLUSION: Epilepsy surgery in our country is an underused therapeutic indication that is not offered or administered to the majority of potential beneficiaries.

TITLE: Estado actual de la cirugía de la epilepsia en España. Compendio y conciencia.Introducción. La epilepsia refractaria al tratamiento médico afecta a entre un tercio y una cuarta parte de los pacientes con epilepsia. Dentro de este grupo, con peor calidad de vida y altos costes sanitarios, existe una considerable proporción de pacientes con causas de epilepsia potencialmente quirúrgicas, y la cirugía de la epilepsia es una opción terapéutica comprobada. En España no sabemos el número real de pacientes que llegan a tratarse en relación con el total de los casos con epilepsia refractaria que podrían beneficiarse del tratamiento quirúrgico. Objetivo. Analizar el número de cirugías de epilepsia realizadas y publicadas en relación con los potenciales casos de epilepsia refractaria candidatos a cirugía en nuestro país. Método. Se realizó una revisión mediante la búsqueda bibliográfica en PubMed y Cochrane de artículos publicados entre 1990 y 2020, combinando las siguientes palabras y operadores booleanos: 'epilepsy surgery IN Spain'. Se clasificaron las evidencias y recomendaciones según los criterios pronósticos del Oxford Center for Evidence Based Medicine (2001) y de la European Federation of Neurological Societies (2004) para actuaciones terapéuticas. Resultados. El 75,6% de las publicaciones se originó en las comunidades autónomas de Madrid y Cataluña. El 46,4% de los artículos publicados son de series cortas. Contabilizamos 2.113 intervenciones quirúrgicas (resecciones, cirugías paliativas, implantación de electrodos profundos e implantación de neuroestimuladores), lo que representa el 8,7% de la población estimada con epilepsia refractaria. Conclusión. La cirugía de la epilepsia en nuestro medio es una indicación terapéutica infrautilizada y que no se ofrece o no se administra a la mayoría de los potenciales beneficiarios.

Impact of adjuvant therapy toxicity on quality of life and emotional symptoms in patients with colon cancer: a latent class analysis.

OBJECTIVE: To identify distinct trajectories of toxicity in colorectal cancer (CRC) patients after adjuvant chemotherapy and its impact on quality of life (QoL) and psychological symptoms. METHODS: A prospective, multicenter study was conducted in 157 patients. A latent class analysis defined the unobserved latent constructs that can be predicted as symptom clusters, considering the intensity of four types of adverse events (AEs). Patients completed EORTC-QLQ-C30, BSI-18, PDRQ-9, and DRS scales. RESULTS: Ninety-six percent had some degree of toxicity, with grades 3-4 being the most common: neurotoxicity (7.2%), hematological (13.1%), digestive (5.2%), and skin toxicity (1.4%). Three distinct latent classes were identified (high [72.5%], mild [16.9%], and low [10.6%] toxicity). Patients with high toxicity had the worst QoL scores and moderately high somatization and psychological distress scores. CONCLUSIONS: Adjuvant chemotherapy for CRC was associated with frequent toxicity that negatively impacted QoL and psychological wellbeing.

Safety and effectiveness of surgery for epilepsy in children. Experience of a tertiary hospital in Ecuador. / Efectividad y seguridad de la cirugía para la epilepsia en niños. Experiencia de un hospital terciario en Ecuador.

INTRODUCTION: There is sufficient evidence on the usefulness of surgery as a therapeutic alternative for patients with drug-resistant epilepsy; however this treatment is underutilized, especially in developing countries. METHODS: We describe the outcomes of epilepsy surgery in 27 paediatric patients at Hospital Baca Ortiz in Quito, Ecuador. Our analysis considered the following variables: reduction in seizure frequency, surgery outcome according to the Engel classification, improvement in quality of life, and serious complications due to surgery. RESULTS: 21 corpus callosotomies and 6 resective surgeries were performed. The mean seizure frequency decreased from 465 per month before surgery to 37.2 per month thereafter (p<.001); quality of life scale scores increased from 12.6 to 37.2 (p<.001), and quality of life improved in 72.7% of patients. Regarding resective surgery, 2 patients with temporal lobe epilepsy and one with posterior quadrant epilepsy achieved Engel class IA, and one patient undergoing hemispherotomy due to Rasmussen encephalitis achieved Engel class IIA. Two patients underwent surgery for hypothalamic hamartoma: one achieved Engel III and the other, Engel IA; however, the latter patient died in the medium term due to a postoperative complication. The other major complication was a case of hydrocephalus, which led to the death of a patient with refractory infantile spasms who underwent corpus callosotomy. CONCLUSIONS: Favourable outcomes were observed in 92.5% of patients.

Facilitating the design of HL7 domain models through a model-driven solution.

BACKGROUND AND GOAL: Health information systems are increasingly sophisticated and developing them is a challenge for software developers. Software engineers usually make use of UML as a standard model language that allows defining health information system entities and their relations. However, working with health system requires learning HL7 standards, that defines and manages standards related to health information systems. HL7 standards are varied, however this work focusses on v2 and v3 since these are the most used one on the area that this work is being conducted. This works aims to allow modeling HL7 standard by using UML. METHODS: Several techniques based on the MDE (Model-Driven Engineering) paradigm have been used to cope with it. RESULTS: A useful reference framework, reducing final users learning curve and allowing modeling maintainable and easy-going health information systems. CONCLUSIONS: By using this approach, a software engineer without any previous knowledge about HL7 would be able to solve the problem of modeling HL7-based health information systems. Reducing the learning curve when working in projects that need HL7 standards.

Coping strategies and depressive symptoms in cancer patients.

INTRODUCTION: Depression in cancer patients is prevalent and negatively impacts their quality of life. Likewise, it correlates with lower overall survival. The aim of this work is to analyze whether different coping strategies, as well as sociodemographic and clinical factors are associated with the presence of depressive symptoms in individuals with a resected, non-metastatic neoplasm about to initiate adjuvant chemotherapy. METHODS: NEOcoping is a cross-sectional, prospective, observational, multicenter study. Clinical (tumor site and stage, time to diagnosis, risk of recurrence, and type of adjuvant treatment) and sociodemographic characteristics (age, gender, marital status, educational level, occupational sector, and employment status), coping strategies (Mini-MAC scale), and depressive symptoms (BSI scale) were collected. A two-block linear regression model was performed to determine the predictive variables of depressive symptoms. RESULTS: 524 adults with resected, non-metastatic cancer were recruited. Twenty-six percent of patients have clinically significant depressive symptoms. Being female, < 40 years of age, having breast and stomach cancer, and > 50% chance of recurrence were associated with increased risk of depression. Likewise, depression was associated with greater helplessness and anxious preoccupation, and less fighting spirit. Age, gender, and risk of recurrence accounted for only 7% of the variance in depressive symptoms. Including coping strategies in the regression analysis significantly increased the variance explained (48.5%). CONCLUSION: Early psychological intervention in patients with maladaptive coping strategies may modulate the onset of depressive symptoms, especially in those at higher risk for depression.

Efficacy of bortezomib to intensify the conditioning regimen and the graft-versus-host disease prophylaxis for high-risk myeloma patients undergoing transplantation.

This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. Patients received fludarabine, melphalan and Bz (days -9 and -2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day -5 and tacrolimus (Tk) from -3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2-4 and 3-4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.

An Ontology-Based Personalized Decision Support System for Use in the Complex Chronically Ill Patient.

Management of the complex chronically ill patient is highly problematic. This is due to the need to complement recommendations in clinical guidelines with recommendations based on treatments performed on a representative set of patients. It is necessary to identify conflicts between the recommendations of different guidelines designed for handling specific chronic diseases. The PITeS-TIiSS project (code PI15/01213) aims to overcome this problem by designing and deploying an ontology-based personalized clinical decision support tool. This helps to improve personalized decisions and reduces variability in clinical practice in an integrated care environment. This paper describes the methodology followed in developing the ontology used to infer clinical knowledge and to develop and implement the support tool. The tool will access the information provided by the Electronic Health Record of Andalusian Health Public Service, the main healthcare provider in a region in Spain with more than eight million inhabitants.

Knowing Patients Better After a Stroke and Secondary Prevention.

The habits and lifestyles are the fundamental factors in the control of cardiovascular risk. Patients who have had a cerebrovascular accident (CVA) have a high risk of having a new event with similar characteristics. The exponentially growing success, penetration and adherence of the new communication technologies, based on applications (APPs), allows to use them to obtain information and influence the risk factors. We propose that empowering patients in their disease can make a more efficient management of it. For this reason, we designed and developed a system which integrates a mobile application and a web application. This system also makes use of peripheral devices to monitor patients and allow the automatic acquisition of information to enable the characterization of this kind of patients in relation to habits and lifestyle. At the same time, the system can also empower these patients with their disease to do secondary prevention.

An Innovative Platform to Analyze Heart Failure Biomarkers in Saliva.

This paper explains a methodology to improve patient safety through early detecting of HF complications and analyzing HF biomarkers in saliva obtained using a biosensor developed in HEARTEN project. A pilot study was performed in two hospitals in Spain and Italy respectively. A direct correlation was identified between TNF-alpha levels in saliva and weight. The weight gain in HF patients could predict a HF decompensation, consequently TNF-alpha could be a new biomarker of these decompensations.

EIP on AHA Ontology for adherence: Knowledge representation advanced tools.

Nowadays diseases tend to chronicle, mainly due to the increase in life expectancy and this leads to a state of polypharmacy. More than 1.5% of Spain's GDP is spent on pharmaceuticals and healthcare products. Complex chronic patients (pluripathological and polymedicated) account for most of the expenditure. The "Action Group A1" of the European Innovation Partnership develops in the "Active and Healthy Ageing" programme actions to improve the quality of life and health outcomes of these patients. On the other hand, the PITeS TIiSS project develops decision support tools to improve this scenario. An ontology has been developed as a tool on adherence. The domain of this ontology is mainly focused on medication adherence and measurement methods. This ontology gathers the necessary knowledge about the domain allowing the use of the ontology as part for is possible.

[Long-term renal function in Wilms tumor survivors]. / Función renal a largo plazo en supervivientes de tumor de Wilms.

OBJETIVE: To evaluate long-term renal function and morbimortality in non-syndromic Wilms tumor (WT) survivors. METHODS: Retrospective study about WT patients treated in 1993-2017, according to SIOP protocols. Mortality, glomerular filtration rate (GFR), prevalence of hypertension and requirement of dialysis and renal transplant were evaluated. Chronic kidney disease (CKD) was defined as GFR <90 ml/min/1.73 m2. RESULTS: Thirty-nine children were treated in the 25 analyzed years. Median time of follow-up was 6 years (0.5-21 years). 48% (19 patients) debuted with stage I or II. Four cases had high-grade histo-logy. Mortality rate was 10%. GFR data were found in 37 patients. Chronic kidney disease (grade I-II) turned up in 6 patients (16%). No patient required renal replacement therapy or renal transplant. 16% of patients developed CKD in both unilateral and bilateral WT, (p>0.05); OR 1.04 (IC 95% 0.09-10.9). Identical results were obtained comparing patients treated with or without radiotherapy (16%). Children with stage I-III had CKD in 11% vs. 40% of patients with stage IV (p=0.12); OR 5.3 (IC 95% 0.61-45). None of them presented hypertension in addition. CONCLUSIONS: In the current study the prevalence of CKD was low but not negligible, although no patients required renal replacement therapy or renal transplant. Bilateral renal involvement and radiotherapy were not associated with CKD development. Metastatic disease determines a higher risk of CKD.

OBJETIVOS: Evaluar la función renal y la morbimortalidad a largo plazo, en supervivientes de tumor de Wilms (TW) no sindrómico. MATERIAL Y METODOS: Estudio retrospectivo de pacientes con TW entre 1993-2017 tratados según protocolos SIOP. Evaluamos mortalidad, filtrado glomerular (FG), prevalencia de hipertensión arterial (HTA), necesidad de diálisis y trasplante renal. Se definió enfermedad renal crónica (ERC) como FG <90 ml/min/1,73 m2. RESULTADOS: En los 25 años analizados se trataron 39 pacientes con edad media diagnóstica de 3,6 años (0,3-11 años). Mediana de seguimiento 6 años (0,5-21 años). El 48% (19 pacientes) debutaron con estadio I o II. Cuatro pacientes presentaron histología de alto riesgo (10%). La mortalidad fue del 10%. El 16% (6 pacientes) desarrolló ERC (grados I-II). Ningún paciente precisó terapia renal sustitutoria (TRS) o trasplante. La presencia de ERC tanto en enfermedad unilateral como bilateral fue del 16%, p>0,05; OR 1,04 (IC 95% 0,09-10,9). Se obtuvieron idénticos resultados (16%) comparando pacientes que recibieron radioterapia frente a aquellos que no. Los pacientes en estadio I, II y III presentaron una prevalencia de ERC del 11% vs. 40% en estadio IV (p=0,12); OR 5,3 (IC 95% 0,61-45). Ningún paciente asoció HTA crónica. CONCLUSIONES: En el presente estudio la prevalencia de ERC en supervivientes de TW no sindrómico es baja pero no desdeñable, aunque ninguno precisó trasplante renal o TRS. La presencia de enfermedad bilateral y la radioterapia no se asociaron al desarrollo de ERC. La enfermedad metastásica condiciona un riesgo mayor de ERC.

[Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index]. / Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso.

TITLE: Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso.

Incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer: data from NEOcoping study.

BACKGROUND: Our study analyzes the incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer. METHODS: A multi-institutional, prospective, observational study was conducted with 750 participants of 14 hospitals in Spain. Participants' socio-demographic and clinical characteristics were collected using a standardized self-report form and using EORTC QoL-QLQ-C30, BSI, Mini-MAC questionnaires. RESULTS: In women, sleep problems, depression and anxious preoccupation were observed in 65, 41 and 21%, respectively. In men, sleep problems, depression and anxious preoccupation were reported in 51, 29 and 61%, respectively. More sleep problems, depression and anxious preoccupation were found among women than males. Depression was a significant predictor of anxious preoccupation. In males, sleep problems partially mediated this association. This was not confirmed in women. CONCLUSION: Our findings point toward the importance of developing interventions that decrease depression and sleep problems in cancer.