[Design of a Tool for Patient Classification Based on Pharmacotherapeutic Attitudes]. / Diseño de una herramienta para la clasificación de pacientes en base a su actitud farmacoterapéutica.

Introduction: Perception and relief of pain exhibit variability among individuals. Age, gender, ethnicity, educational level, actual stress level, mood, or medical conditions can modify the personal interpretation of pain and responses to pharmacological treatment. These differences may play a significant role in the effects, sometimes unwanted, of analgesic treatment. Objectives: Define patient typologies with Failed Back Syndrome regarding attitudes toward the disease, treatment, healthcare, and the follow-up they receive from their healthcare professionals. Create a tool for patient profile identification. Materials and Methods: A clinical case series study, observational, descriptive, and cross-sectional. Study population: patients from the Pain Unit of Nuestra Señora de La Candelaria University Hospital (HUNSC) in Tenerife, conducted in three phases: collection of medical history data (F0), initial visit (F1), and personal interview (F2). Results: Five patient typologies are obtained based on responses to 17 items. Regression equations are calculated from these responses to predict the patient type. They are grouped into "Classics," "Dependents," "Critics," "Unconscious," and "Responsible." Additionally, two tools with 17 items and another with 7 optimized items are developed to simplify the process. Conclusions: These tools enable Community Pharmacy (CP) to identify patients based on their characteristics to direct personalized strategies for each of them.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

[Myasthenia gravis. Update on diagnosis and therapy]. / Miastenia gravis. Actualización diagnóstica y terapéutica.

Myasthenia gravis is an autoimmune disease caused by the presence of specific antibodies targeting different postsynaptic components of the neuromuscular junction, and is clinically characterized by the presence of fatigueable muscle weakness. In the etiopathogenesis plays a central role the thymus and the most frequently detected pathogenic autoantibodies are targeted to the acetylcholine receptor. The increase in the knowledge of the immunological components of the neuromuscular junction in the last two decades has been fundamental to identify new pathogenic antibodies, reduce the percentage of patients with seronegative myasthenia, and propose a classification of patients into subgroups with clinical-therapeutic interest. In addition, in recent years, new drugs have been developed for the treatment of patients with myasthenia gravis that are refractory to conventional immunosuppressive treatment.

Mental Health, Burnout, and Resilience in Healthcare Professionals After the First Wave of COVID-19 Pandemic in Spain: A Longitudinal Study.

OBJECTIVE: This study aims to examine whether there are differences in symptoms of posttraumatic stress, depression, anxiety, levels of burnout and resilience in Spanish healthcare staff between the first wave of the COVID-19 pandemic and after it, depending on several demographic and work-related variables. METHODS: A longitudinal study was conducted in April 2020 (T0), and July 2020 (T1). Symptoms of posttraumatic stress, depression, anxiety, burnout, levels of resilience, along with demographic and work-related variables in 443 workers were assessed. RESULTS: Symptoms and burnout were more pronounced at T0, whereas the levels of resilience were higher at T1. Being women, being young, holding a lower-level job, less years of experience, lower educational level, and/or working rotating shifts are associated with having more posttraumatic stress symptoms and burnout. CONCLUSION: These variables would be considered in similar situations.

Negative frequency-dependent selection maintains shell banding polymorphisms in two marine snails (Littorina fabalis and Littorina saxatilis).

The presence of shell bands is common in gastropods. Both the marine snails Littorina fabalis and Lttorina saxatilis are polymorphic for this trait. Such polymorphism would be expected to be lost by the action of genetic drift or directional selection, but it appears to be widespread at relatively constant frequencies. This suggests it is maintained by balancing selection on the trait or on a genetically linked trait. Using long time series of empirical data, we compared potential effects of genetic drift and negative frequency-dependent selection (NFDS) in the two species. The contribution of genetic drift to changes in the frequency of bands in L. fabalis was estimated using the effective population size estimated from microsatellite data, while the effect of genetic drift in L. saxatilis was derived from previously published study. Frequency-dependent selection was assessed by comparing the cross-product estimator of fitness with the frequency of the polymorphism across years using a regression analysis. Both studied species showed patterns of NFDS. In addition, in L. fabalis, contributions from genetic drift could explain some of the changes in banding frequency. Overdominance and heterogeneous selection did not fit well to our data. The possible biological explanations resulting in the maintenance of the banding polymorphism are discussed.

Design and flight results of the VHF/UHF communication system of Longjiang lunar microsatellites.

As a part of China's Chang'e-4 lunar far side mission, two lunar microsatellites for low frequency radio astronomy, amateur radio and education, Longjiang-1 and Longjiang-2, were launched as secondary payloads on 20 May 2018 together with the Queqiao L2 relay satellite. On 25 May 2018, Longjiang-2 successfully inserted itself into a lunar elliptical orbit of 357 km × 13,704 km, and became the smallest spacecraft which entered lunar orbit with its own propulsion system. The satellite carried the first amateur radio communication system operating in lunar orbit, which is a VHF/UHF software defined radio (SDR) designed for operation with small ground stations. This article describes and evaluates the design of the VHF/UHF radio and the waveforms used. Flight results of the VHF/UHF radio are also presented, including operation of the radio, performance analysis of downlink signals and the first lunar orbit UHF very-long-baseline interferometry (VLBI) experiment.

DECORE-21: Assessment of occupational stress in police. Confirmatory factor analysis of the original model.

There is scarce research on stress in Spanish police officers and on the use of instruments to assess this construct in this professional group. In Spain, the DECORE questionnaire has been one of the most used. Nevertheless, it had not been previously applied to police officers. The aim of this study was to analyze both the construct validity and the reliability of the original model of 44 items. A cross-sectional design and a non-probabilistic quota sampling were used. A total of 223 Spanish police officers participated. 202 police personnel were men (90.6%) and 21 were women (9.4%). The average age was 41 years old (SD = 7.52). These police officers answered the DECORE questionnaire. Confirmatory Factor Analysis was carried out. The results showed an unsatisfactory adjustment using the original model of 44 items. A final solution of 21 items and four factors was formulated with both suitable validity and reliability indexes. In this model, 23 items that did not weigh highly in any of the four factors were removed. The DECORE-21 questionnaire is recommended to assess work-related stress in police officers.

MSP22.8 is a protease inhibitor-like protein involved in shell mineralization in the edible mussel Mytilus galloprovincialis.

The mussel shell protein 22.8 (MSP22.8) is recognized by a monoclonal antibody (M22.8) directed against larvae of the mussel Mytilus galloprovincialis. After being secreted by cells of the mantle-edge epithelium into the extrapallial (EP) space (the gap between the mantle and the shell), the protein is detected in the extrapallial fluid (EPF) and EP hemocytes and finally becomes part of the shell matrix framework in adult specimens of M. galloprovincialis. In the work described here, we show how MSP22.8 is detected in EPF samples from different species of mussels (M. galloprovincialis, Mytilus edulis, and Xenostrobus securis), and also as a shell matrix protein in M. galloprovincialis, Mytilus chilensis, and Perna canaliculus. A multistep purification strategy was employed to isolate the protein from the EPF, which was then analyzed by mass spectrometry in order to identify it. The results indicate that MSP22.8 is a serpin-like protein that has great similarity with the protease inhibitor-like protein-B1, reported previously for Mytilus coruscus. We suggest that MSP22.8 is part of a system offering protection from proteolysis during biomineralization and is also part of the innate immune system in mussels.

A novel method for estimating the strength of positive mating preference by similarity in the wild.

Mating preference can be a driver of sexual selection and assortative mating and is, therefore, a key element in evolutionary dynamics. Positive mating preference by similarity is the tendency for the choosy individual to select a mate which possesses a similar variant of a trait. Such preference can be modelled using Gaussian-like mathematical functions that describe the strength of preference, but such functions cannot be applied to empirical data collected from the field. As a result, traditionally, mating preference is indirectly estimated by the degree of assortative mating (using Pearson's correlation coefficient, r) in wild captured mating pairs. Unfortunately, r and similar coefficients are often biased due to the fact that different variants of a given trait are nonrandomly distributed in the wild, and pooling of mating pairs from such heterogeneous samples may lead to "false-positive" results, termed "the scale-of-choice effect" (SCE). Here we provide two new estimators of mating preference (Crough and Cscaled) derived from Gaussian-like functions which can be applied to empirical data. Computer simulations demonstrated that r coefficient showed robust estimations properties of mating preference but it was severely affected by SCE, Crough showed reasonable estimation properties and it was little affected by SCE, while Cscaled showed the best properties at infinite sample sizes and it was not affected by SCE but failed at biological sample sizes. We recommend using Crough combined with the r coefficient to infer mating preference in future empirical studies.

Characterization of a Monoclonal Antibody Directed against Mytilus spp Larvae Reveals an Antigen Involved in Shell Biomineralization.

The M22.8 monoclonal antibody (mAb) developed against an antigen expressed at the mussel larval and postlarval stages of Mytilus galloprovincialis was studied on adult samples. Antigenic characterization by Western blot showed that the antigen MSP22.8 has a restricted distribution that includes mantle edge tissue, extrapallial fluid, extrapallial fluid hemocytes, and the shell organic matrix of adult samples. Other tissues such as central mantle, gonadal tissue, digestive gland, labial palps, foot, and byssal retractor muscle did not express the antigen. Immunohistochemistry assays identified MSP22.8 in cells located in the outer fold epithelium of the mantle edge up to the pallial line. Flow cytometry analysis showed that hemocytes from the extrapallial fluid also contain the antigen intracellularly. Furthermore, hemocytes from hemolymph have the ability to internalize the antigen when exposed to a cell-free extrapallial fluid solution. Our findings indicate that hemocytes could play an important role in the biomineralization process and, as a consequence, they have been included in a model of shell formation. This is the first report concerning a protein secreted by the mantle edge into the extrapallial space and how it becomes part of the shell matrix framework in M. galloprovincialis mussels.

[Delirium Prevention]. / Prevención del delirium.

INTRODUCTION: Delirium is the most prevalent neuropsychiatric syndrome in the general hospital. Its presence is a marker of poor prognosis for patients. Its prevention could be the most effective strategy for reducing its frequency and its complications. OBJECTIVE: To review recent findings and strategies for the prevention of delirium. METHODOLOGY: A non-systematic review of scientific articles published in the last ten years in Spanish and English. A search was made in databases such as MEDLINE, Cochrane, EMBASE, Ovid, and ScienceDirect, for articles that included the terms, delirium and prevention. RESULTS: Identification of predisposing and precipitating factors for delirium and a better understanding of the pathophysiological mechanisms underlying the onset of delirium have enabled the implementation of various pharmacological and non-pharmacological strategies in patients at high risk to develop hospital delirium. The studies to prevent delirium have focused on surgical patients. The current evidence supports the daily implementation of non-pharmacological measures to prevent delirium, as they are easy and cost effective. The available evidence is still limited to recommend the daily use of pharmacological strategies in delirium prophylaxis, and there is a consensus against the modest use of antipsychotic drugs in surgical patients and dexmedetomidine in patients in intensive care. CONCLUSIONS: New high-quality clinical trials and studies involving non-surgical patients are needed to provide more evidence about this subject.

Prevención del delirium / Delirium Prevention

Introducción: El delirium es el síndrome neuropsiquiátrico más prevalente en el hospital general. Su presencia es un marcador de mal pronóstico para los pacientes. Prevenirlo puede ser la estrategia más efectiva para reducir su frecuencia y sus complicaciones. Objetivo: Identificar estrategias farmacológicas y no farmacológicas para la prevención del delirium. Metodología: Revisión no sistemática, en bases de datos como MEDLINE, Cochrane, EMBASE, Ovid y ScienceDirect, de artículos en español y en inglés publicados en los últimos diez arios, mediante una búsqueda que incluyó los términos delirium AND prevention. Resultados: La identificación de los factores predisponentes y precipitantes del delirium y una mayor comprensión de los mecanismos fisiopatológicos que subyacen a la aparición de este han permitido implementar diversas estrategias farmacológicas y no farmacológicas para pacientes con alto riesgo de contraer delirium hospitalario. Los estudios para prevenir el delirium se han concentrado en pacientes quirúrgicos. La evidencia actual apoya la implementación sistemática de medidas no farmacológicas para la prevención del delirium, por tratarse de estrategias fáciles de implementar y costo-efectivas. La evidencia disponible todavía es poca para recomendar el uso sistemático de medicamentos profilácticos para delirium, si bien existe consenso frente a la modesta utilidad de los antipsicóticos en pacientes quirúrgicos y de la dexmedetomidina en pacientes de cuidados intensivos. Conclusiones: Se necesitan nuevos ensayos clínicos de alta calidad que aporten mayor evidencia e incluyan a pacientes no quirúrgicos.

Introduction: Delirium is the most prevalent neuropsychiatric syndrome in the general hospital. Its presence is a marker of poor prognosis for patients. Its prevention could be the most effective strategy for reducing its frequency and its complications. Objective: To review recent findings and strategies for the prevention of delirium. Methodology: A non-systematic review of scientific articles published in the last ten years in Spanish and English. A search was made in databases such as MEDLINE, Cochrane, EMBASE, Ovid, and ScienceDirect, for articles that included the terms, delirium and prevention. Results: Identification of predisposing and precipitating factors for delirium and a better understanding of the pathophysiological mechanisms underlying the onset of delirium have enabled the implementation of various pharmacological and non-pharmacological strategies in patients at high risk to develop hospital delirium. The studies to prevent delirium have focused on surgical patients. The current evidence supports the daily implementation of non-pharmacological measures to prevent delirium, as they are easy and cost effective. The available evidence is still limited to recommend the daily use of pharmacological strategies in delirium prophylaxis, and there is a consensus against the modest use of antipsychotic drugs in surgical patients and dexmedetomidine in patients in intensive care. Conclusions: New high-quality clinical trials and studies involving non-surgical patients are needed to provide more evidence about this subject.

The scale-of-choice effect and how estimates of assortative mating in the wild can be biased due to heterogeneous samples.

The mode in which sexual organisms choose mates is a key evolutionary process, as it can have a profound impact on fitness and speciation. One way to study mate choice in the wild is by measuring trait correlation between mates. Positive assortative mating is inferred when individuals of a mating pair display traits that are more similar than those expected under random mating while negative assortative mating is the opposite. A recent review of 1134 trait correlations found that positive estimates of assortative mating were more frequent and larger in magnitude than negative estimates. Here, we describe the scale-of-choice effect (SCE), which occurs when mate choice exists at a smaller scale than that of the investigator's sampling, while simultaneously the trait is heterogeneously distributed at the true scale-of-choice. We demonstrate the SCE by Monte Carlo simulations and estimate it in two organisms showing positive (Littorina saxatilis) and negative (L. fabalis) assortative mating. Our results show that both positive and negative estimates are biased by the SCE by different magnitudes, typically toward positive values. Therefore, the low frequency of negative assortative mating observed in the literature may be due to the SCE's impact on correlation estimates, which demands new experimental evaluation.

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41% of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.