[Chronic communicable and non-communicable pathology and skin pathology of the migrant patient]. / Enfermedad crónica transmisible y no transmisible, y enfermedad cutánea del paciente migrante.

The care of migrant patients includes initial screening and lifelong monitoring, highlighting the importance of preventing and tracking chronic, communicable and non-communicable diseases. The prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity varies by ethnicity, influenced by genetic factors, lifestyle, and socio-economic status. Preventive measures, health promotion, and risk factor identification are crucial. Chronic communicable diseases may manifest years after transmission, underscoring the necessity of primary care screening, especially for populations from endemic or high-risk areas. Imported skin lesions are a common reason for consultation among migrant and traveller patients. Their ethiology is varied, ranging from common conditions such as scabies, mycoses, and urticaria to tropical dermatoses like filariasis and leprosy.

Order in chaos: Structure of chaotic invariant sets of square-wave neuron models.

Bursting phenomena and, in particular, square-wave or fold/hom bursting, are found in a wide variety of mathematical neuron models. These systems have different behavior regimes depending on the parameters, whether spiking, bursting, or chaotic. We study the topological structure of chaotic invariant sets present in square-wave bursting neuron models, first detailed using the Hindmarsh-Rose neuron model and later exemplary in the more realistic model of a leech heart neuron. We show that the unstable periodic orbits that form the skeleton of the chaotic invariant sets are deeply related to the spike-adding phenomena, typical from these models, and how there are specific symbolic sequences and a symbolic grammar that organize how and where the periodic orbits appear. Linking this information with the topological template analysis permits us to understand how the internal structure of the chaotic invariants is modified and how more symbolic sequences are allowed. Furthermore, the results allow us to conjecture that, for these systems, the limit template when the small parameter ε, which controls the slow gating variable, tends to zero is the complete Smale topological template.

Dynamical analysis of early afterdepolarization patterns in a biophysically detailed cardiac model.

Arrhythmogenic early afterdepolarizations (EADs) are investigated in a biophysically detailed mathematical model of a rabbit ventricular myocyte, providing their location in the parameter phase space and describing their dynamical mechanisms. Simulations using the Sato model, defined by 27 state variables and 177 parameters, are conducted to generate electrical action potentials (APs) for different values of the pacing cycle length and other parameters related to sodium and calcium concentrations. A detailed study of the different AP patterns with or without EADs is carried out, showing the presence of a high variety of temporal AP configurations with chaotic and quasiperiodic behaviors. Regions of bistability are identified and, importantly, linked to transitions between different behaviors. Using sweeping techniques, one-, two-, and three-parameter phase spaces are provided, allowing ascertainment of the role of the selected parameters as well as location of the transition regions. A Devil's staircase, with symbolic sequence analysis, is proposed to describe transitions in the ratio between the number of voltage (EAD and AP) peaks and the number of APs. To conclude, the obtained results are linked to recent studies for low-dimensional models and a conjecture is made for the internal dynamical structure of the transition region from non-EAD to EAD behavior using fold and cusp bifurcations and maximal canards.

Primary Care Physicians Can Comprehensively Manage Patients with Sleep Apnea. A Noninferiority Randomized Controlled Trial.

Rationale: General practitioners play a passive role in obstructive sleep apnea (OSA) management. Simplification of the diagnosis and use of a semiautomatic algorithm for treatment can facilitate the integration of general practitioners, which has cost advantages.Objectives: To determine differences in effectiveness between primary health care area (PHA) and in-laboratory specialized management protocols during 6 months of follow-up.Methods: A multicenter, noninferiority, randomized, controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in six tertiary hospitals in Spain. Sequentially screened patients with an intermediate to high OSA probability were randomized to PHA or in-laboratory management. The PHA arm involved a portable monitor with automatic scoring and semiautomatic therapeutic decision-making. The in-laboratory arm included polysomnography and specialized therapeutic decision-making. Patients in both arms received continuous positive airway pressure treatment or sleep hygiene and dietary treatment alone. The primary outcome measure was the Epworth Sleepiness Scale. Secondary outcomes were health-related quality of life, blood pressure, incidence of cardiovascular events, hospital resource utilization, continuous positive airway pressure adherence, and within-trial costs.Measurements and Main Results: In total, 307 patients were randomized and 303 were included in the intention-to-treat analysis. Based on the Epworth Sleepiness Scale, the PHA protocol was noninferior to the in-laboratory protocol. Secondary outcome variables were similar between the protocols. The cost-effectiveness relationship favored the PHA arm, with a cost difference of €537.8 per patient.Conclusions: PHA management may be an alternative to in-laboratory management for patients with an intermediate to high OSA probability. Given the clear economic advantage of outpatient management, this finding could change established clinical practice.Clinical trial registered with www.clinicaltrials.gov (NCT02141165).

ATYPICAL PRESENTATION OF CRYPTOCOCCUS NEOFORMANS IN A KOALA (PHASCOLARCTOS CINEREUS): A MAGNETIC RESONANCE IMAGING AND COMPUTED TOMOGRAPHY STUDY.

Cryptococcosis is a worldwide and potentially fatal mycosis documented in wild and captive koalas ( Phascolarctos cinereus ) caused by Cryptococcus neoformans . Though mainly a subclinical disease, when the nasal cavity is affected, epistaxis, mucopurulent nasal discharge, dyspnea, and facial distortion may occur. This report describes a case of cryptococcosis in a koala where unilateral exophthalmos was the only evident clinical sign and magnetic resonance imaging and computed tomography findings are described. Both advanced imaging techniques should be considered as standard and complementary techniques for nasal cavity evaluation in koalas.

[Coping and subjective burden in primary caregivers of dependent elderly relatives in Andalusia, Spain]. / Afrontamiento y carga subjetiva en cuidadores primarios de adultos mayores dependientes de Andalucía, España.

PURPOSE: To analyse the relationship between the type of coping and subjective burden in caregivers of dependent elderly relatives in Andalusia (Spain). DESIGN: Cross-sectional study. LOCATION: Primary Health Care (autonomous community of Andalusia, Spain). PARTICIPANTS: A convenience sample of 198 primary caregivers of dependent elderly relatives. KEY MEASUREMENTS: Coping (Brief COPE), subjective burden (caregiver stress index), objective burden (functional capacity [Barthel Index], cognitive impairment [Pfeiffer Test], behavioural problems of the care recipient [Neuropsychiatric Inventory], and caregivers' dedication to caring), gender and kinship. RESULTS: Most caregivers were women (89.4%), daughters of the care recipient (57.1%), and shared home with him/her (69.7%). On controlling for objective burden, gender and kinship, it was found that subjective burden was positively associated with dysfunctional coping (ß=0.28; P<.001) and negatively with emotion-focused coping (ß=-0.25; P=.001), while no association was found with problem-focused coping. CONCLUSIONS: Dysfunctional coping may be a risk factor for subjective burden, and emotion-focused coping may be a protective factor for that subjective burden regardless of the objective burden, and gender and kinship of the caregivers.

Macro- and micro-chaotic structures in the Hindmarsh-Rose model of bursting neurons.

We study a plethora of chaotic phenomena in the Hindmarsh-Rose neuron model with the use of several computational techniques including the bifurcation parameter continuation, spike-quantification, and evaluation of Lyapunov exponents in bi-parameter diagrams. Such an aggregated approach allows for detecting regions of simple and chaotic dynamics, and demarcating borderlines-exact bifurcation curves. We demonstrate how the organizing centers-points corresponding to codimension-two homoclinic bifurcations-along with fold and period-doubling bifurcation curves structure the biparametric plane, thus forming macro-chaotic regions of onion bulb shapes and revealing spike-adding cascades that generate micro-chaotic structures due to the hysteresis.

Video-EEG in the first 24 hours after the first unprovoked seizure in patients with normal neurological examination and head CT scan.

PURPOSE: to determine the yield of Video-Electroencephalogram (VEEG) in the first 24 h in patients with a first unprovoked seizure and normal neurological examination, laboratory findings, and cranial CT scans. METHODS: we analyzed retrospectively the yield of VEEG performed in these patients in the emergency department. All the patients were subsequently seen in the Epilepsy Clinic, and the epilepsy diagnosis was confirmed. RESULTS: we included 19 patients who met the inclusion criteria; all of them underwent VEEG with the 10-20 system within the first 24 h after the seizure. The duration of the recordings averaged at 108.53 min and may or may not have included intermittent photic stimulation and sleep recording; 74% of the recordings were abnormal, with 26% being normal. Among the abnormal cases, epileptogenic activity was found in 47% and seizures in 26% of the patients; because both findings could be present in the same VEEG, 63% of all the VEEG showed epileptogenic alterations or seizures. The VEEG anomalies were recorded before the 20th minute (standard VEEG duration) in 58% of patients who exhibited epileptogenic activity and/or seizures, and after the 20th minute in 42%. CONCLUSION: conducting approximately 100-minute VEEGs within the first 24 h after a first unprovoked seizure can enhance the diagnostic yield in patients with epilepsy. However, the study has the limitations of its sample size and retrospective nature.

Dynamical mechanism for generation of arrhythmogenic early afterdepolarizations in cardiac myocytes: Insights from in silico electrophysiological models.

We analyze the dynamical mechanisms underlying the formation of arrhythmogenic early afterdepolarizations (EADs) in two mathematical models of cardiac cellular electrophysiology: the Sato et al. biophysically detailed model of a rabbit ventricular myocyte of dimension 27 and a reduced version of the Luo-Rudy mammalian myocyte model of dimension 3. Based on a comparison of the two models, with detailed bifurcation analysis using spike-counting techniques and continuation methods in the simple model and numerical explorations in the complex model, we locate the point where the first EAD originates in an unstable branch of periodic orbits. These results serve as a basis to propose a conjectured scheme involving a hysteresis mechanism with the creation of alternans and EADs in the unstable branch. This theoretical scheme fits well with electrophysiological experimental data on EAD generation and hysteresis phenomena. Our findings open the door to the development of novel methods for pro-arrhythmia risk prediction related to EAD generation without actual induction of EADs.

Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential.

The problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive ability of the peak reduction potentials. In the work described here a series of fourteen chloride Pt(II) and Pt(IV) compounds was synthesised and fully characterised. The compounds contain different bidentate arylazole heterocyclic ligands. Their cytotoxic properties against human lung carcinoma (A549), human breast carcinoma (MCF7) and human colon carcinoma (HCT116 and HT29) cell lines were studied. A clear relationship between the type of ligand and the anti-proliferative properties was found, with the best results obtained for the Pt(II) compound that contains an aniline fragment, (13), thus evidencing a positive effect of the NH2 group. Stability and aquation studies in DMSO, DMF and DMSO/water mixtures were carried out on the active complexes and an in-depth analysis of the two aquation processes, including DFT analysis, of 13 was undertaken. It was verified that DNA was the target and that cell death occurred by apoptosis in the case of 13. Furthermore, the cytotoxic derivatives did not exhibit haemolytic activity. The reduction of the Pt(IV) compounds whose Pt(II) congeners were active was studied by several techniques. It was concluded that the peak reduction potential was not useful to predict the ability for reduction. However, a correlation between the cytotoxic activity and the standard reduction potential was found.

Exercise and Use of Enhancement Drugs at the Time of the COVID-19 Pandemic: A Multicultural Study on Coping Strategies During Self-Isolation and Related Risks.

Introduction: Little is known about the impact of restrictive measures during the COVID-19 pandemic on self-image and engagement in exercise and other coping strategies alongside the use of image and performance-enhancing drugs (IPEDs) to boost performance and appearance. Objectives: To assess the role of anxiety about appearance and self-compassion on the practice of physical exercise and use of IPEDs during lockdown. Methods: An international online questionnaire was carried out using the Exercise Addiction Inventory (EAI), the Appearance Anxiety Inventory (AAI), and the Self-Compassion Scale (SCS) in addition to questions on the use of IPEDs. Results: The sample consisted of 3,161 (65% female) adults from Italy (41.1%), Spain (15.7%), the United Kingdom (UK) (12.0%), Lithuania (11.6%), Portugal (10.5%), Japan (5.5%), and Hungary (3.5%). The mean age was 35.05 years (SD = 12.10). Overall, 4.3% of the participants were found to engage in excessive or problematic exercise with peaks registered in the UK (11.0%) and Spain (5.4%). The sample reported the use of a wide range of drugs and medicines to boost image and performance (28%) and maintained use during the lockdown, mostly in Hungary (56.6%), Japan (46.8%), and the UK (33.8%), with 6.4% who started to use a new drug. Significant appearance anxiety levels were found across the sample, with 18.1% in Italy, 16.9% in Japan, and 16.7% in Portugal. Logistic regression models revealed a strong association between physical exercise and IPED use. Anxiety about appearance also significantly increased the probability of using IPEDs. However, self-compassion did not significantly predict such behavior. Anxiety about appearance and self-compassion were non-significant predictors associated with engaging in physical exercise. Discussion and Conclusion: This study identified risks of problematic exercising and appearance anxiety among the general population during the COVID-19 lockdown period across all the participating countries with significant gender differences. Such behaviors were positively associated with the unsupervised use of IPEDs, although no interaction between physical exercise and appearance anxiety was observed. Further considerations are needed to explore the impact of socially restrictive measures among vulnerable groups, and the implementation of more targeted responses.

Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review. / La estimulación cerebral profunda en el trastorno obsesivo-compulsivo refractario al tratamiento: una revisión sistemática.

INTRODUCTION: At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. METHOD: We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. RESULTS: The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. CONCLUSIONS: The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit.

An alternative approach to GTV margin determination in stereotactic body radiotherapy.

PURPOSE: This study aims to estimate a realistic margin in stereotactic body radiotherapy (SBRT) through examining the determination uncertainties of gross tumour volume (GTV). METHODS: Three computed tomography (CT) scans were performed on each patient in different sessions as a treatment simulation. Registration of the different CT image sets was based on the fiducial marks from two stereotactic guides. GTV was defined in each one of them, as well as both the encompassing (UNI) and overlapping (INT) volumes. This protocol was altered following imaging guided radiotherapy (IGRT) implementation, so tumour displacements could be corrected for. The patient was scanned without repositioning solely considering tumour intrafraction variations. In addition, isocentre and dimension variations were obtained for each patient and cohort. A Monte Carlo code was developed to simulate tumour volume, considering them as ellipsoids in order to study their behaviour. Lastly, the equivalent radius (R eq) was defined for each of these volumes, experimental and simulated, and both and values were derived by simple linear regression to the mean value . RESULTS: The global margin M can be defined as this systematic error plus an additional residual random uncertainty, with values M = 3.4 mm for Body Frame, M = 2.3 mm for BodyFIX and M = 2.1 mm without repositioning. The experimental results obtained are in good agreement with simulated values, validating the use of the Monte Carlo code to calculate a margin formula. CONCLUSIONS: Introducing IGRT is not enough to obtain a zero margin; consequently, the safety margin, dependent on tumour shape and size dispersion, can be evaluated using this formulation.

Evaluation of the Spanish hot dip galvanising sector as a source of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.

A survey to estimate the polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) emissions of Spanish hot dip galvanising sector was carried out during 2002. This investigation is the first presenting Spanish experimental data related to this industrial sector. Three different matrices: flue gas, ash and filter dust were tested to quantify the PCDD/Fs generated during the galvanising process. The organic source of PCDD/F formation could be from the insufficient degreasing o from inhibitors or additives used in the pickling steps such as quinoline, isoquinoline, 8-methylquinoline or polyether phosphoric acid. Low levels PCDD/Fs were achieved in air emissions when air control devices are used. On the contrary, filter dusts are highly contaminated; indicating that the absence of air control devices would increase the risk of fugitive emissions. Homologue profiles and Principal Component Analysis demonstrate there are differences in the formation mechanisms in the bath zone (ashes) compared to the stack location (filter dusts and air emissions), related to the de novo synthesis and reaction time. The annual PCDD/F emission to the atmosphere for this sector during 2002 has been estimated in 0.023g I-TEQ. The emission factor of plants with air control devices has been calculated at 0.030microg I-TEQ/ton of galvanised steel.

Bone mineral density evolution in young premenopausal women with idiopathic osteoporosis.

Idiopathic osteoporosis is a frequent cause of osteoporosis in young premenopausal women. However, there are no data about the treatment of these patients. The aim of this study was to analyse the evolution of bone mineral density (BMD) in premenopausal women with idiopathic osteoporosis treated with a conservative approach. Retrospective study of 16 premenopausal women with idiopathic osteoporosis (aged 35.7+/-7 years) with a mean follow-up period of 3 years (1-6 years). BMD measurements at the lumbar spine and femoral neck were obtained in all patients at baseline and yearly (patients had one or more fragility fractures and/or a Z score < -2 in the lumbar spine or femur). Secondary causes of osteoporosis were excluded in all patients. Patients were treated with calcium and vitamin D to achieve a calcium intake of up to 1,500 mg/day and were advised to increase physical activity. A significant increase in lumbar and femoral BMD was observed after 2 and 3 years of follow-up, respectively (1.9+/-1.9% mean increase in lumbar spine, p= 0.021, at 2 years) (5.6+/-4.5% mean increase in femur, p=0.04, at 3 years). The serum total alkaline phosphatase (TAP) values increased at 2 years (122+/-46 vs 140+/-36 U/l, p=0.054). In addition, a negative correlation between baseline TAP serum values and lumbar BMD evolution at 2 years was observed (r=-0.748, p=0.013). No patient developed new skeletal fractures during the follow-up period. In young premenopausal women with idiopathic osteoporosis the conservative treatment with supplements of calcium and vitamin D associated with an increase of physical activity is associated with an increase in BMD without evidence of further skeletal fractures after more than 3 years of follow-up.

Camptocormia as a clinical manifestation of mitochondrial myopathy.

Camptocormia is an unusual condition characterized by a progressive weakness of the extensor muscles of the spine that cause an involuntary truncal flexion. Occasionally, camptocormia can be the clinical manifestation of an underlying myopathy, including inflammatory or metabolic myopathies. We present a case of a 78-year-old female with camptocormia associated with a mitochondrial myopathy. Additionally, we review the clinical characteristics of three similar, previously reported cases.

RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis.

BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis. Retinoic acid inducible-gene I (RIG-I), a receptor of innate immunity that promotes type I interferon, was observed in perifascicular areas in DM. We compared the value of RIG-I expression with perifascicular atrophy as a biomarker of DM. METHODS: We studied by immunohistochemical analysis the expression of RIG-I and the presence of perifascicular atrophy in 115 coded muscle biopsies: 44 patients with DM, 18 with myositis with overlap, 8 with ASS, 27 with non-DM inflammatory myopathy (16 with polymyositis, 6 with inclusion body myositis, 5 with immune-mediated necrotizing myopathy), 8 with muscular dystrophy (4 with dysferlinopathy, 4 with fascioscapulohumeral muscle dystrophy) and 10 healthy controls. RESULTS: We found RIG-I-positive fibers in 50% of DM samples vs 11% in non-DM samples (p < 0.001). Interestingly, RIG-I staining identified 32% of DM patients without perifascicular atrophy (p = 0.007). RIG-I sensitivity was higher than perifascicular atrophy (p < 0.001). No differences in specificity between perifascicular atrophy and RIG-I staining were found (92% vs 88%). RIG-I staining was more reproducible than perifascicular atrophy (κ coefficient 0.52 vs 0.37). CONCLUSIONS: The perifascicular pattern of RIG-I expression supports the diagnosis of DM. Of importance for clinical and therapeutic studies, the inclusion of RIG-I in the routine pathological staining of samples in inflammatory myopathy will allow us to gather more homogeneous subgroups of patients in terms of immunopathogenesis.

Recomendaciones sobre estudios neurofisiológicos en tiempos de pandemia de COVID-19 / Recommendations on neurophysiological studies during the COVID-19 pandemic

A finales de enero, la Organización Mundial de la Salud declaró el brote actual de la enfermedad por coronavirus COVID-19 como emergencia de salud pública de importancia internacional. En España, desde que el 14 de marzo de 2020 el Gobierno decretase el estado de alarma, los médicos encargados de las pruebas neurofisiológicas las hemos estado realizando sin tener un criterio consensuado ni unas pautas adecuadas de seguridad claras para los facultativos, los técnicos ni los pacientes. Las siguientes recomendaciones, basadas en el actual conocimiento de la enfermedad y, por tanto, susceptibles de variaciones en el futuro, se proponen cuando la pandemia parece que ha entrado en un proceso de disminución de la virulencia y, con ello, las medidas estrictas de confinamiento hasta ahora mantenidas; sin embargo, ante la posibilidad de una segunda oleada de rebrotes de la pandemia, parece necesario establecer unas recomendaciones básicas y de mínimos para respetar el derecho del paciente a una atención adecuada, similar a la previa a la pandemia, y mantener unos mínimos de seguridad para los propios pacientes y los médicos, técnicos y personal sanitario que realizan estas pruebas. Se trata de recomendaciones sobre el establecimiento de una prioridad basándose en el motivo de consulta, el establecimiento de llamadas de comprobación de la situación clínica del paciente antes de acudir a la consulta externa y las normas de ejecución de las pruebas neurofisiológicas, que se basan, en general, en la preservación de circuitos hospitalarios, el respeto y el cuidado de las barreras de contagio conocidas de esta enfermedad, y la utilización de material desechable. Estas recomendaciones son de especial interés, sobre todo por la incertidumbre de no saber la evolución de la infección por el SARS-CoV-2 en las próximas semanas o meses

At the end of January, the current outbreak of COVID-19 coronavirus disease was declared an important international public health emergency. In Spain, since the government declared the state of alarm on 14 March 2020, doctors responsible for carrying out neurophysiological tests have been performing them without any consensus criterion or clear safety guidelines for doctors, technicians or patients. The following recommendations, based on current knowledge of the disease and therefore liable to change in the future, are proposed when the pandemic appears to have entered a process of decreasing virulence and, with it, the strict containment measures established to date. However, in view of the possibility of a second wave of the pandemic, it seems necessary to establish basic and minimum recommendations to respect the patient's right to appropriate care, similar to that provided prior to the pandemic, and to maintain minimum safety standards for the patients themselves and for the doctors, technicians and health personnel carrying out these tests. These recommendations concern the constitution of a priority based on the reason for consultation, the establishment of calls to check the patient's clinical situation before going to the outpatient department and the rules for carrying out neurophysiological tests, which are generally based on the preservation of hospital circuits, respect for and observation of the known barriers to contagion of this disease, and the use of disposable material. These recommendations are of particular interest, especially given the uncertainty of not knowing the evolution of the SARS-CoV-2 infection in the coming weeks or months

Pro-Oxidant Activity of Amine-Pyridine-Based Iron Complexes Efficiently Kills Cancer and Cancer Stem-Like Cells.

Differential redox homeostasis in normal and malignant cells suggests that pro-oxidant-induced upregulation of cellular reactive oxygen species (ROS) should selectively target cancer cells without compromising the viability of untransformed cells. Consequently, a pro-oxidant deviation well-tolerated by nonmalignant cells might rapidly reach a cell-death threshold in malignant cells already at a high setpoint of constitutive oxidative stress. To test this hypothesis, we took advantage of a selected number of amine-pyridine-based Fe(II) complexes that operate as efficient and robust oxidation catalysts of organic substrates upon reaction with peroxides. Five of these Fe(II)-complexes and the corresponding aminopyridine ligands were selected to evaluate their anticancer properties. We found that the iron complexes failed to display any relevant activity, while the corresponding ligands exhibited significant antiproliferative activity. Among the ligands, none of which were hemolytic, compounds 1, 2 and 5 were cytotoxic in the low micromolar range against a panel of molecularly diverse human cancer cell lines. Importantly, the cytotoxic activity profile of some compounds remained unaltered in epithelial-to-mesenchymal (EMT)-induced stable populations of cancer stem-like cells, which acquired resistance to the well-known ROS inducer doxorubicin. Compounds 1, 2 and 5 inhibited the clonogenicity of cancer cells and induced apoptotic cell death accompanied by caspase 3/7 activation. Flow cytometry analyses indicated that ligands were strong inducers of oxidative stress, leading to a 7-fold increase in intracellular ROS levels. ROS induction was associated with their ability to bind intracellular iron and generate active coordination complexes inside of cells. In contrast, extracellular complexation of iron inhibited the activity of the ligands. Iron complexes showed a high proficiency to cleave DNA through oxidative-dependent mechanisms, suggesting a likely mechanism of cytotoxicity. In summary, we report that, upon chelation of intracellular iron, the pro-oxidant activity of amine-pyrimidine-based iron complexes efficiently kills cancer and cancer stem-like cells, thus providing functional evidence for an efficient family of redox-directed anti-cancer metallodrugs.

Trastornos del movimiento y de la conducta durante el sueño en el adulto / Sleep-related movement and behavioural disorders in adults

Los trastornos del movimiento y de la conducta durante el sueño pueden tener un impacto en la calidad del sueño del paciente y dar lugar a síntomas diurnos. En estos grupos de enfermedades se incluyen entidades como el síndrome de piernas inquietas, los movimientos periódicos de las piernas y las parasomnias del sueño de movimientos oculares rápidos (REM) y no REM. El conocimiento de sus características clínicas y nociones sobre su manejo es de gran importancia para el neurólogo y especialista en sueño por su frecuencia e impacto en la calidad del sujeto. Con frecuencia, estos pacientes son referidos a dichos especialistas, y es relevante conocer que ciertos trastornos del sueño pueden asociarse a otras enfermedades neurológicas

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions