Symptoms in Swiss adolescents in relation to exposure from fixed site transmitters : a prospective cohort study

There is public concern regarding potential health effects of radiofrequency electromagnetic fields (RF-EMF) emitted by fixed site transmitters. We therefore investigated whether self-reported general well-being in adolescents is affected by RF-EMF exposure from mobile phone base stations (downlink) and broadcast transmitters (TV and radio).; In a prospective cohort study, 439 study participants aged 12-17 years, completed questionnaires about their self-reported well-being and possible confounding factors at baseline and one year later. Exposure from fixed site transmitters at home and school was calculated by using a geospatial propagation model. Data were analysed using a mixed-logistic cross-sectional model of a combined dataset consisting of baseline and follow-up data and a longitudinal approach where we investigated whether exposure at baseline (cohort analysis) or changes in exposure between baseline and follow-up (change analysis) were related to a new onset of a symptom between baseline and follow-up. All analyses were adjusted for relevant confounders.; Mean exposure (median; 75(th)) for broadcast transmitters, downlink and total exposure at baseline were 1.9 μW/m(2) (1.0 μW/m(2); 2.8 μW/m(2)), 14.4 μW/m(2) (3.8 μW/m(2); 11.0 μW/m(2)) and 16.3 μW/m(2) (5.8 μW/m(2); 13.4 μW/m(2)), respectively. In cross-sectional analyses no associations were observed between any symptom and RF-EMF exposure from fixed site transmitters. In the cohort and change analyses only a few significant associations were observed including an increased OR for tiredness (2.94, 95%CI: 1.43 to 6.05) for participants in the top 25(th) percentile of total RF-EMF exposure from fixed site transmitters at baseline, in comparison to participants exposed below the median and a decreased OR for exhaustibility (0.50, 95%CI: 0.27 to 0.93) for participants with an exposure increase between baseline and follow-up.; In this cohort study, using a geospatial propagation model, RF-EMF exposure from fixed site transmitters was not consistently associated with self-reported symptoms in Swiss adolescents. The few observed associations have to be interpreted with caution and might represent chance findings

miRNAs in protection and regeneration of dopaminergic midbrain neurons

PD is the second most frequent neurodegenerative disorder affecting over 3 % of the population older than 80 years of age. Although PD is a system disorder which affects most regions of the brain, the progressive demise of the nigrostriatal projections and the inability of this system to regenerate are mainly responsible for the functional deficits observed. The etiology underlying PD is not finally resolved. Recent studies suggest that gene expression regulators might contribute to a large variety of disease states. miRNAs are small non-coding RNAs that are important for the post-transcriptional regulation of gene expression. Alterations in miRNA function have been reported in different neurodegenerative diseases including PD. Furthermore, miRNAs are auspicious therapeutic targets, as the manipulation of their expression might be neuroprotective or could induce the regeneration of neurons. In the present study the miRNAome of developing PMN cultures was analyzed and it was demonstrated that the major changes occur during early development. In order to analyze miRNA expression changes during degeneration and spontaneous regeneration of the murine nigrostriatal system a small RNA sequencing of the midbrain of the 6-OHDA mouse model for PD was performed and revealed novel sets of miRNAs involved in degeneration and regeneration of DA neurons in vivo. Taken together, miRNAs play an important role in development, maintenance and degeneration of DA neurons in vivo and in vitro and thus are promising targets for a better understanding of PD pathophysiology and the development of new therapeutic strategies

Deformations of local Artin rings via Hilbert-Burch matrices

In the local setting, Gr\"obner cells are affine spaces that parametrize ideals in $\mathbf{k}[\![x,y]\!]$ that share the same leading term ideal with respect to a local term ordering. In particular, all ideals in a cell have the same Hilbert function, so they provide a cellular decomposition of the punctual Hilbert scheme compatible with its Hilbert function stratification. We exploit the parametrization given in \cite{HW21} via Hilbert-Burch matrices to compute the Betti strata, with hands-on examples of deformations that preserve the Hilbert function, and revisit some classical results along the way. Moreover, we move towards an explicit parametrization of all local Gr\"obner cells.Comment: 18 page

Brentuximab-Induced Peripheral Neurotoxicity: A Multidisciplinary Approach to Manage an Emerging Challenge in Hodgkin Lymphoma Therapy

Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate approved to treat classical Hodgkin lymphoma (HL). BV-induced peripheral neurotoxicity (BVIN) is one of the greatest concerns for haematologists treating HL for several reasons. First, BVIN is highly frequent. Most patients receiving BV will experience some degree of BVIN, resulting in the primary reason for dose modification or discontinuation of HL therapy. Second, BV produces sensory, motor, and/or autonomic peripheral nerve dysfunction, which can present as severe, disabling forms of BVIN-predominantly motor-in some patients. Third, although largely reversible, BVIN may persist months or years after treatment and thereby become a major issue in HL survivorship. BVIN may, therefore, negatively affect the quality of life and work-life of often young patients with HL, in whom long-term survival is expected. Currently, the only strategy for BVIN includes dose adjustments and treatment discontinuation; however, this could interfere with LH therapy efficacy. In this setting, early recognition and adequate management of BVIN are critical in improving clinical outcomes. Careful neurologic monitoring may allow accurate diagnoses and gradation of ongoing forms of BVIN presentation. This review analysed current, available data on epidemiology, pathophysiology, patient- and treatment-related risk factors, clinical and neurophysiologic phenotypes, and management in patients with HL. Furthermore, this review specifically addresses limitations posed by BVIN assessments in clinical practice and provides skills and tools to improve neurologic assessments in these patients. Integrating this neurotoxic drug in clinical practice requires a multidisciplinary approach to avoid or minimise neurotoxicity burden in survivors of HL

Problematic mobile phone use of Swiss adolescents : is it linked with mental health or behaviour?

To investigate the associations between problematic mobile phone use and mental health and behavioural problems in 412 Swiss adolescents owning a mobile phone while controlling for amount of mobile phone use.; Problematic mobile phone use was determined by the MPPUS-10 (Mobile Phone Problem Use Scale) and related to health and behavioural problems by means of multivariable regression modelling.; MPPUS-10 was 4.7 (95 % CI 1.8, 7.6) units higher in girls than in boys, increased significantly with age and was significantly decreased with increasing educational level of the parents. Furthermore, problematic mobile phone use was associated with impaired psychological well-being, impaired parent and school relationships and more behavioural problems but was not related to peer support and social acceptance.; Our study indicates that problematic mobile phone use is associated with external factors such as worse home and school environment and internal factors such as impaired mental health and behavioural problems of the adolescents and thus problematic mobile phone use should be addressed, in particular when dealing with adolescents showing behavioural or emotional problems

Conocimientos y actitudes de los profesionales de los equipos de atención primaria sobre el documento de voluntades anticipadas

ResumenObjetivoDescribir el estado actual de los conocimientos sobre el documento de voluntades anticipadas (DVA) de los profesionales de atención primaria.EmplazamientoSAP Mataró Maresme del Institut Català de la Salut.DiseñoEstudio descriptivo y transversal.ParticipantesProfesionales de los equipos de atención primaria.MedicionesSe diseñó un cuestionario de autorrespuesta individual y anónima. Se definió un patrón de respuesta y un patrón de respuesta mínima correcta para cada bloque. Se realizan 2 pruebas de comprensibilidad y validez de los conceptos, y una prueba piloto de factibilidad.Resultados principalesSobre una población diana de 475 individuos se obtienen 227 respuestas (47%), de las que 219 (46%) fueron válidas. Según los colectivos profesionales, el 59% son médicos, el 28% son pediatras, el 7% son odontólogos, el 59% son diplomados en enfermería, el 12% son auxiliares de enfermería, el 30% son trabajadores sociales y el 25% son de atención al usuario. Solo 4 profesionales tienen redactado su propio DVA. El porcentaje de aciertos por bloques es el siguiente: el 83,8% de definición, el 4,1% de aspectos legales, el 0,5% de procedimiento-registro, el 1,4% de contenidos y el 38,6% de aplicación.ConclusionesLos profesionales tienen un conocimiento general sobre qué son las voluntades anticipadas y el DVA, pero saben poco de la normativa, el contenido y el registro. No hay diferencias significativas entre los colectivos analizados. El cuestionario parece útil para evaluar los conocimientos sobre el DVA.AbstractObjectiveTo assess the current state of knowledge and attitudes on the advance directives (living wills) document of professionals working in primary.DesignDescriptive, cross-sectional study.ParticipantsPrimary care professionals.SettingCatalonia Health Institute, Maresme Province, Barcelona.MethodsAn anonymous self-administered questionnaire was prepared with a correct answer model and a minimum correct level for each block of questions, as well as two comprehensibility and validity tests and a pilot feasibility test.ResultsFrom a target population of 475 individuals, t 227 (47%) responses were received (59% of GPs, 28% of paediatricians, 7% of dentists, 59% of nurses, 12% of assistant clinics, 30% of social workers and 25% of administrative assistants). Four people had written their own advance directive document. The percentage of correct answers was: definition block 83.8%, legal aspects 4.1%, procedure-register 0.5%; content 1.4%, application 38.6%.ConclusionsPrimary care workers have a general knowledge on the advance directives and the advance directive document but not enough about the law, content and registers. There was no significant difference between professional groups. The questionnaire appears useful for assessing knowledge on advance directives document

siRNA-silencing of CD40 attenuates unilateral ureteral obstruction-induced kidney injury in mice

Ureteral obstruction; CD40; MiceObstrucción ureteral; CD40; RatonesObstrucció ureteral; CD40; RatolinsBACKGROUND: The costimulatory CD40-CD40L pathway plays a role in kidney inflammation. We have previously reported that renal CD40 upregulation precedes cellular interstitial infiltrate and fibrosis in the unilateral ureteral obstruction (UUO) model. Here we sought to evaluate whether the administration of siRNA-CD40 has a therapeutic effect in a reversible unilateral ureteral obstruction (D-UUO) mice model. METHODS: Eight week-old C57BL6J male mice were divided into four groups: Vehicle (Phosphate-buffered saline) (n = 8); siRNA SC (non-specific siRNA) (n = 6); siRNA-CD40 (n = 8) and WT (wild type) (n = 6) mice. UUO was performed with a microvascular clamp. At day 3 after surgery, the ureteral clamp was removed and nephrectomy of the contralateral kidney was performed. Immediately, PBS, siRNA SC (50μg) or siRNA-CD40 (50μg) was administrated via the tail vein. Mice were killed 48h hours after the siRNA or saline administration. Wild type (WT) mice were used as controls. Blood samples were collected for measuring creatinine and blood urea nitrogen (BUN). Histology and kidney mRNA expression were performed. RESULTS: The administration of siRNA-CD40 reduced significantly the severity of acute renal failure associated with UUO. Pathologic analysis showed reduction of tubular dilation, interstitial fibrosis, F4/80 macrophage and CD3 (T cell) infiltration in animals treated with siRNA-CD40. Furthermore, kidney mRNA gene expression analysis showed significantly lower levels of macrophage markers (F4/80 and Mannose receptor), fibrosis matrix proteins (Fibronectin, MMP-9, Collagen IV and α-SMA), pro-inflammatory cytokines (iNOS and MCP-1) and the pro-fibrotic molecule TGF-β1 in siRNA-CD40. CONCLUSIONS: The administration of siRNA-CD40 therapy reduces the severity of the acute kidney injury induced by obstructive uropathy and promotes kidney repair. This strategy seems suitable to be tested in humans.Funded by Instituto de Salud Carlos III through the project RD16/0009/ 0003 (Co-funded by European Regional Development Fund. ERDF, a way to build Europe

Experimentant els avantatges del treball en grup del professorat

La constitució d'un grup de treball estable entre professors especialistes permet introduir innovacions en la pràctica docent de manera eficaç. La cooperació entre centres propers per realitzar activitats experimentals de llarg abast resol molts dels problemes de caràcter pràctic que sorgeixen en els centres de secundària

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

Chimeric antigen receptor (CAR) T-cell systemic immunotherapy has revolutionized how clinicians treat several refractory and relapsed hematologic malignancies. Due to its peculiar mechanism of action, CAR T-cell-based therapy has enlarged the spectrum of neurological toxicities. CAR T-cell-associated neurotoxicity-initially defined as CAR T-cell-related encephalopathy syndrome (CRES) and currently coined within the acronym ICANS (immune effector cell-associated neurotoxicity syndrome)-is perhaps the most concerning toxicity of CAR T-cell therapy. Importantly, hematologic malignancies (especially lymphoid malignancies) may originate in or spread to the central nervous system (CNS) in the form of parenchymal and/or meningeal disease. Due to the emergence of deadly and neurological adverse events, such as fatal brain edema in some patients included in early CAR T-cell trials, safety concerns for those with CNS primary or secondary infiltration arose and contributed to the routine exclusion of individuals with pre-existing or active CNS involvement from pivotal trials. However, based primarily on the lack of evidence, it remains unknown whether CNS involvement increases the risk and/or severity of CAR T-cell-related neurotoxicity. Given the limited treatment options available for patients once they relapse with CNS involvement, it is of high interest to explore the role of novel clinical strategies including CAR T cells to treat leukemias/lymphomas and myeloma with CNS involvement. The purpose of this review was to summarize currently available neurological safety data of CAR T-cell-based immunotherapy from the clinical trials and real-world experiences in adult patients with CNS disease due to lymphoma, leukemia, or myeloma. Increasing evidence supports that CNS involvement in hematologic disease should no longer be considered per se as an absolute contraindication to CAR T-cell-based therapy. While the incidence may be high, severity does not appear to be impacted significantly by pre-existing CNS status. Close monitoring by trained neurologists is recommended