Harmful Ostreopsis cf. ovata blooms could extend in time span with climate change in the Western Mediterranean Sea.

Fast environmental changes and high coastal human pressures and impacts threaten the Mediterranean Sea. Over the last decade, recurrent blooms of the harmful dinoflagellate Ostreopsis cf. ovata have been recorded in many Mediterranean beaches. These microalgae produce toxins that affect marine organisms and human health. Understanding the environmental conditions that influence the appearance and magnitude of O. cf. ovata blooms, as well as how climate change will modify its future distribution and dynamics, is crucial for predicting and managing their effects. This study investigates whether the spatio-temporal distribution of this microalga and the frequency of its blooms could be altered in future climate change scenarios in the Mediterranean Western basin. For the first time, an ecological habitat model (EHM) is forced by physico-chemical climate change simulations at high-resolution, under the strong greenhouse gas emission trajectory (RCP8.5). It allows to characterize how O. cf. ovata may respond to projected conditions and how its distribution could shift over a wide spatial scale, in this plausible future. Before being applied to the EHM, future climate simulations are further refined by using a statistical adaptation method (Cumulative Distribution Function transform) to improve the predictions robustness. Temperature (optimum 23-26 °C), high salinity (>38 psu) and high inorganic nutrient concentrations (nitrate >0.25 mmol N·m-3 and phosphate >0.035 mmol P·m-3) drive O. cf. ovata abundances. High spatial disparities in future abundances are observed. Namely, O. cf. ovata abundances could increase on the Mediterranean coasts of France, Spain and the Adriatic Sea while a decrease is expected in the Tyrrhenian Sea. The bloom period could be extended, starting earlier and continuing later in the year. From a methodological point of view, this study highlights best practices of EHMs in the context of climate change to identify sensitive areas for current and future harmful algal blooms.

[Synthetic indicator of compliance with standards for Quality Units of health centers and multicenter prospective pilot study]. / Indicador sintético de cumplimiento de estándares para Unidades de Calidad de centros sanitarios y estudio de pilotaje prospectivo multicéntrico.

BACKGROUND AND OBJECTIVE: In Spain, Quality Units play a key and unique role in advising healthcare centers on the methodology of healthcare quality. The objectives of the study were to develop computer algorithms to obtain a synthetic indicator of standard compliance for Quality Units and to pilot its functioning in these units. MATERIALS AND METHODS: The Excel program was used to establish evaluation algorithms, and quantitatively interrelate and weight various categories of standards, as a computer evaluation tool, to build a continuous improvement cycle system, and offer a global synthetic indicator of compliance. The tool was tested in a prospective multicenter pilot study, in which coordinators of Quality Units from different health centers and care settings participated, to evaluate the usefulness of the tool and compliance with the standards, in addition to analyzing the content validity of each standard. RESULTS: The formulas for the structured computer algorithms were developed, consecutively, in a «PLAN-DO-CHECK-ACT¼ improvement cycle for the 9 categories of standards, resulting in a single synthetic indicator of compliance. Twenty-one Quality Units participated in the piloting. The overall average compliance rate for the synthetic indicator was 55.63% with differences between centers (P=.002) and between categories (P<.0001), but not by autonomous communities (P=.86) or by areas (P=.97). Content validity was ensured through the variable of «understanding¼ of the standards (P<.001), and through their «justification¼ with documentary evidence (P<.001). CONCLUSIONS: The computer tool with the synthetic indicator have allowed for the evaluation of standard compliance in Quality Units of healthcare centers.

[Development and validation of standards for quality units of health centers]. / Desarrollo y validación de estándares para unidades de calidad de centros sanitarios.

OBJECTIVE: In Spain, the Quality Units advise health centres, services and professionals on the methodology of continuous improvement of the quality of care. A system based on good practice standards could provide these units with a tool to improve their results and value their work. The objective was to develop, agree on and validate standards, to properly guide and orient the functions, results and continuous improvement of the Quality Units in health centers. MATERIAL AND METHODS: A qualitative-quantitative, prospective and cross-sectional study was carried out, applying the Metaplan method, the e-Delphi technique and a simulation study. The participants were coordinators of these units, belonging to 14 Spanish Autonomous Communities and distributed in four experts' panels. They agreed on the standards to be used and evaluated the different types of validity. RESULTS: The 204 standards proposed by the scientific committee were reduced to 157 with Metaplan, to 110 with e-Delphi, and to 96 with the committee's final review (87.3% consensus, content validity). The construct validity showed a Cronbach's alpha >0.7 (P<.001); the validity of content was reaffirmed in the simulation workshop (80% "understood" each other, P<.001; and there was "documentary evidence" in 84%, P<.001); face validity was accepted (75% "related to quality dimensions", P<.001); and the validity of the criteria was verified with a sensitivity of 84.2%, a specificity of 98.3%, and a kappa index of 0.84. CONCLUSIONS: Valid standards have been developed for Quality Units in health centers.

The Alien Flora of Australia (AFA), a unified Australian national dataset on plant invasion.

Biological invasions are a major threat to Australia. Information on alien flora in Australia is collated independently by different jurisdictions, which has led to inconsistencies at the national level, hampering efficient management. To harmonise different information sources, we present the Alien Flora of Australia (AFA), a nationally unified dataset. To create the AFA, we developed an R script that compares existing data sources (the Australian Plant Census and state and territory censuses), identifies mismatches among them and integrates the information into unified invasion statuses at the national scale. The AFA follows the taxonomy and nomenclature adopted for the Australian Plant Census, introduction status and impact of plants known to occur in Australia. The up-to-date information presented in this dataset can aid early warning of alien species invasions, facilitate decision-making at different levels, and biosecurity at national scale. The associated script is ready to be implemented into new versions of the AFA with updated releases of any of the data sources, streamlining future efforts to track of alien flora across Australia.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Emerging Hyalomma lusitanicum: From identification to vectorial role and integrated control.

In the Mediterranean basin, the tick species Hyalomma lusitanicum Koch stands out among other species of the Hyalomma genus due to its wide distribution, and there is great concern about its potential role as a vector and/or reservoir and its continuous expansion to new areas because of climate warming and human and other animal movements. This review aims to consolidate all the information on H. lusitanicum, including taxonomy and evolution, morphological and molecular identification, life cycle, sampling methods, rearing under laboratory conditions, ecology, hosts, geographical distribution, seasonality, vector role and control methods. The availability of adequate data is extremely relevant to the development of appropriate control strategies in areas where this tick is currently distributed as well as in new areas where it could become established in the near future.

[Influence of physical activity on radiotherapy-treated breast cancer patients: A systematic review]. / Influencia del ejercicio físico sobre los síntomas de la radioterapia en pacientes con cáncer de mama: revisión sistemática.

INTRODUCTION: The number of survivors with cancer is growing worldwide, but the adverse effects of the radiotherapy are still frequent, affecting effort capacity, respiratory function and quality of life. The objective is to know how the physical exercise influences the respiratory function and tolerance to effort, in pacients with breast cancer after the radiotherapy treatment. MATERIALS AND METHODS: The searches were carried out in the databases of Pubmed, PEDro, Web Of Science, Cochrane, EMBASE, UptoDate and Tripdatabase. Were included studies with patients with breast cancer treated with radiotherapy and included in an exercise program. The main results were: maximum oxygen consumption, 6 minutes walking test, forced vital capacity, vital capacity, forced expiratory volume in 1 second, total lounge capacity, inspiratory capacity, and the diffusion capacity of the lungs for carbon monoxide. RESULTS: The results show an increase of the effort capacity with 15% improvements in the maximum oxygen consumption and 6.675% in the 6 minutes walking test, while they are limited for the respiratory function. CONCLUSIONS: The physical exercise is effective for improve the effort capacity in pacients with breast cancer treated with radiotherapy, without changes in the respiratory function. Nevertheless, new studies are necessary to investigate deeply how the physical exercise influences in those pacients, and the ideal design of the programs.

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic NSCLC.

INTRODUCTION: Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed. PATIENTS AND METHODS: The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis. RESULTS: The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient's sera inhibited the EGFR pathway in tumor cells growing in vitro. CONCLUSIONS: Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.

Internet, video game and mobile phone addiction in children and adolescents diagnosed with ADHD: A case-control study. / Adicción a Internet, videojuegos y teléfonos móviles en niños y adolescentes: Un estudio de casos y controles.

The use of new technologies has become widespread worldwide. There is increasing concern about "Internet addiction disorder" (IAD), "Internet gaming disorder" (IGD), and "Mobile phone addiction" (MPA). Attention Deficit Hyperactivity Disorder (ADHD) has been associated with IAD and IGD. However, evidence is lacking about the relationship between ADHD and MPA. Naturalistic case-control study. 112 patients (51 children with and 61 children without ADHD) between 7 and 17 years old were compared regarding IAD, IGD, and MPA. We used the TEA questionnaire for the assessment of executive function and ADHD (ATENTO), and the ADITEC questionnaire to get gender-differentiated information for IAD, IGD, and MPA. Female children scored higher on MPA (Mean ± Standard Deviation, M ± SD) (25.93 ±  17.64 vs. 14.77 ±  19.43, p=0.03), while male children scored higher on IGD (30.09 ± 21.65 vs. 12.51 ± 16.61, p < 10^-3). Severity of hyperactivity/impulsivity and IGD were moderately correlated (r=0.349, p=0.013), but the correlation disappeared after controlling for the impact on the social domain as measured by the ATENTO questionnaire (r=171, p=0.250). Most parents are concerned that their children may be addicted to IAD/IGD/MPA. Female gender is associated with MPA, while male gender is associated with IGD. ADHD is a risk factor for developing IAD and IGD. Combined type and predominantly hyperactive/impulsive ADHD are each associated with IGD. Good social adjustment protects against developing IGD. There are gender vulnerabilities for IAD/IGD/MPA. ADHD is a risk factor for IGD, but good social adjustment buffers this association.

El uso de las nuevas tecnologías se ha generalizado a nivel mundial. Hay una creciente preocupación respecto del «trastorno de adicción a Internet¼ (TAI), el «trastorno de juego en Internet¼ (TJI) y la «adicción al teléfono móvil¼ (ATM). El trastorno por el déficit de atención con hiperactividad (TDAH) se ha asociado con el TAI y el TJI. Sin embargo, falta evidencia sobre la relación entre el TDAH y la ATM. Estudio naturalista de casos y controles. Comparación de 112 pacientes (51 niños con el TDAH y 61 niños sin el TDAH) con edades entre 7-17 años respecto del TAI, el TJI y la ATM. Utilizamos el cuestionario de TEA para evaluar la función ejecutiva y el TDAH (ATENTO) y el cuestionario ADITEC para obtener información diferenciada por género para el TAI, el TJI y la ATM. Las niñas obtuvieron puntuaciones más altas en la ATM (desviación típica ± media, DT ± M) (25,93 ± 17,64 vs. 14,77 ± 19,43, p = ,03), mientras que los niños obtuvieron puntuaciones más altas en el TJI (30,09 ± 21,65 vs. 12,51 ± 16,61, p < 10

[Moyamoya disease: revision and description of a number of pedriatic cases]. / Enfermedad de moyamoya: descripción de una serie de casos pediátricos.

INTRODUCTION: Moyamoya disease is caused because of progressive occlusion of the arterial circle of Willis, leading to a compensatory net-like abnormal vessels development. The objective is to describe the number of cases in our center (tertiary hospital). PATIENTS AND METHODS: Retrospective study. Revision of pediatric medical histories diagnosed of moyamoya disease or moyamoya syndrome (in case of predisposing disease) between 2005 and 2018. Demographic variables were collected, related to diagnosis, risk factors, treatment, and follow-up. RESULTS: Seven cases were collected with a median age of 6 years and an equitable distribution by sex. Five associated predisposing pathologies (Down syndrome, neurofibromatosis, sickle cell disease, Behcet). The main clinical diagnosis was neurological focus (five cases), followed by epileptic seizures (four), and headache (two). One was asymptomatic at diagnosis. Six strokes were documented, five of them were isquemic. The arteriography (goldstardard) was made in five patients. Five presented bilateral involvement of the vessels, the internal carotid arteries and the middle cerebral arteries were the most affected. Six received acetylsalicylic acid treatment and five of them required antiepileptic drugs. Revascularization surgery (encephaloduroarteriomyosinangiosis) was performed in four patients, and in one, strokes persisted. The most prevalent sequelae were hemiparesis and psychomotor retardation. CONCLUSIONS: The risk factors presented in our patients match to those described in the literature. The symptoms at the onset can be diverse and ischemic strokes predominate in our series. Revascularization surgery was effective in more than half of the cases. Subsequent follow-up is necessary to assess complications and sequelae.

TITLE: Enfermedad de moyamoya: descripción de una serie de casos pediátricos.Introducción. La enfermedad de moyamoya se produce por la oclusión de las arterias alrededor del polígono de Willis y genera una amplia red de vasos colaterales. El objetivo es describir la serie histórica de nuestro centro (hospital terciario). Pacientes y métodos. Es un estudio retrospectivo. Se hizo una revisión de historias clínicas de pacientes pediátricos diagnosticados de enfermedad o síndrome de moyamoya (si patología predisponente) entre 2005 y 2018. Se recogieron variables demográficas, relacionadas con el diagnóstico, factores de riesgo, tratamiento y seguimiento. Resultados. Se obtuvieron siete casos, con una mediana de edad de seis años y distribución por sexos equitativa. Cinco asociaban patologías predisponentes (síndrome de Down, neurofibromatosis, drepanocitosis y Behçet). La clínica predominante en el diagnóstico fue focalidad neurológica (cinco casos), seguida de crisis epilépticas (cuatro) y cefalea (dos). Un paciente era asintomático en el momento del diagnóstico. Se documentaron seis ictus, cinco de los cuales fueron isquémicos. La arteriografía (técnica de referencia) constaba en cinco pacientes. Cinco presentaban afectación bilateral y estaban mayormente afectadas las arterias carótidas internas y las cerebrales medias. Seis recibieron tratamiento con ácido acetilsalicílico y cinco necesitaron fármacos antiepilépticos. La cirugía de revascularización (encefaloduroarteriomiosinangiosis) se realizó en cuatro pacientes y en uno persistieron los ictus. Las secuelas más prevalentes fueron hemiparesia y retraso psicomotor. Conclusiones. Los factores de riesgo presentados en nuestros pacientes se ajustan a los descritos en la bibliografía. La clínica en el inicio puede ser diversa y predominan los ictus isquémicos en nuestra serie. La cirugía de revascularización fue efectiva en más de la mitad de los casos. Es necesario un seguimiento posterior para evaluar complicaciones y secuelas.

Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

[Proposals by the Spanish Society of Quality in Healthcare (SECA) for the recovery of the National Health Service after the COVID-19 pandemic]. / Propuestas de la SECA para la recuperación del Sistema Nacional de Salud tras la pandemia por SARS-CoV-2.

BACKGROUND: The SARS-CoV-2 pandemic has demanded responses for which the National Health System (NHS) was not prepared. The Spanish Society for Quality in Healthcare (SECA) has the mission of promoting quality in healthcare and contributing to its proper functioning. OBJECTIVE: To present SECA recommendations to ensure the quality and safety of patients in the recovery of the NHS following the impact of the SARS-CoV-2 pandemic and the possibility of a resurgence. METHODS: Qualitative study to seek consensus with the participation of 49 representatives of the different stakeholders (patients, managers, professionals, academics and researchers). The areas to be explored were: lessons learned, management of new care demands from COVID-19 patients, recompositing of templates, strengthening the resilience of professionals, new role of patients and contingency plans. RESULTS: Four hundred and twenty-eight proposals were submitted. Once duplicates were deleted and similar proposals were merged, their number was reduced to 120. Of these, 60 proposals were prioritized and grouped into two categories of measures: (1) to recover the Health System (equity, accessibility, effectiveness, efficiency, safety, patient experience and work morale) and (2) to deal with possible outbreaks. CONCLUSION: SECA responds to its commitment to society with recommendations to ensure quality of healthcare and patient safety in the COVID-19 Era.

[Megalencephalic leukoencephalopathy with cysts -the clinical importance in the genetic era]. / Leucoencefalopatía megalencefálica con quistes: importancia de la descripción clínica en la era genética.

INTRODUCTION: Megalencephalic leukoencephalopathy with cysts is a leukodystrophy of genetic origin that produces an alteration in the water and ion homeostasis in the brain, generating vacuolar forms and chronic oedema in the white matter with progressive neurological deterioration. It should be suspected in infants who present progressive macrocephaly during the first year of life, motor retardation and characteristic findings in magnetic resonance brain scans. CASE REPORT: We report the case of a girl who was followed up from the age of 9 months due to progressive macrocephaly and delayed psychomotor development and brain MRI findings consistent with megalencephalic leukoencephalopathy with cysts, and the appearance of epilepsy during its development. The usual genetic studies (new generation sequencing and array) were negative, but as the diagnostic criteria were met, a complementary messenger RNA and DNA study was conducted, which confirmed the presence of two pathogenic variants in MLC1. CONCLUSIONS: Megalencephalic leukoencephalopathy with cysts is a rare condition. Progressive macrocephaly in the first year of life, the absence of deterioration or slow deterioration, and the possibility of developing epilepsy, spasticity and ataxia are characteristic signs in its course. It is important for these patients to undergo an imaging test that shows findings that characterise this condition, which, together with the clinical features, makes it possible to differentiate it from other leukodystrophies and to establish a confirmatory diagnosis. Genetic studies can confirm the associated mutation that makes it possible to predict the clinicoradiological phenotype.

TITLE: Leucoencefalopatía megalencefálica con quistes: importancia de la descripción clínica en la era genética.Introducción. La leucoencefalopatía megalencefálica con quistes es una leucodistrofia de origen genético que produce una alteración de la homeostasis del agua e iones en el cerebro, generando formas vacuolares y edema crónico en la sustancia blanca con deterioro neurológico progresivo. Debe sospecharse en los lactantes que presentan macrocefalia progresiva durante el primer año de vida, retraso motor y hallazgos característicos en la resonancia magnética cerebral. Caso clínico. Niña en seguimiento desde los 9 meses por macrocefalia progresiva y retraso del desarrollo psicomotor con presencia en la resonancia magnética cerebral de hallazgos compatibles con leucoencefalopatía megalencefálica con quistes, y aparición de epilepsia en su evolución. Los estudios genéticos habituales (secuenciación de nueva generación y array) fueron negativos, pero, al cumplir los criterios diagnósticos, se procedió al estudio del ARN mensajero y el ADN complementario, que confirmó la presencia de dos variantes patogénicas en MLC1. Conclusiones. La leucoencefalopatía megalencefálica con quistes es una entidad infrecuente. Es característica la macrocefalia progresiva en el primer año de vida, la ausencia de deterioro o deterioro lento, y la posibilidad de desarrollar epilepsia, espasticidad y ataxia en su evolución. Cobra importancia en dichos pacientes la realización de una prueba de imagen que muestre hallazgos propios de la entidad, lo que, junto con la clínica, permite diferenciarla de otras leucodistrofias y establecer un diagnóstico confirmatorio. Los estudios genéticos pueden constatar la mutación asociada que posibilita predecir el fenotipo clinicorradiológico.

Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

Combined effects of land-use intensification and plant invasion on native communities.

Land-use intensification (LUI) and biological invasions are two of the most important global change pressures driving biodiversity loss. However, their combined impacts on biological communities have been seldom explored, which may result in misleading ecological assessments or mitigation actions. Based on an extensive field survey of 445 paired invaded and control plots of coastal vegetation in SW Spain, we explored the joint effects of LUI (agricultural and urban intensification) and invasion on the taxonomic and functional richness, mean plant height and leaf area of native plants. Our survey covered five invasive species with contrasting functional similarity and competitive ability in relation to the native community. We modeled the response of native communities for the overall and invader-specific datasets, and determined if invader-native functional differences could influence the combined impacts of LUI and invasion. Overall, we found that urban intensification reduced taxonomic richness more strongly at invaded plots (synergistic interactive effects). In contrast, functional richness loss caused by urban intensification was less pronounced at invaded plots (antagonistic interactive effects). Overall models showed also that urban intensification led to reduced mean leaf area, while agriculture was linked to higher mean plant height. When exploring invader-specific models, we observed that the combined effects of agricultural and urban intensification with invasion were heterogeneous. At invaded plots, invader-native functional differences accounted for part of this variability. Our findings demonstrate the importance of considering the interactive effects of global change pressures for a better assessment and management of ecosystems.

Highly integrated workflows for exploring cardiovascular conditions: Exemplars of precision medicine in Alzheimer's disease and aortic dissection.

For precision medicine to be implemented through the lens of in silico technology, it is imperative that biophysical research workflows offer insight into treatments that are specific to a particular illness and to a particular subject. The boundaries of precision medicine can be extended using multiscale, biophysics-centred workflows that consider the fundamental underpinnings of the constituents of cells and tissues and their dynamic environments. Utilising numerical techniques that can capture the broad spectrum of biological flows within complex, deformable and permeable organs and tissues is of paramount importance when considering the core prerequisites of any state-of-the-art precision medicine pipeline. In this work, a succinct breakdown of two precision medicine pipelines developed within two Virtual Physiological Human (VPH) projects are given. The first workflow is targeted on the trajectory of Alzheimer's Disease, and caters for novel hypothesis testing through a multicompartmental poroelastic model which is integrated with a high throughput imaging workflow and subject-specific blood flow variability model. The second workflow gives rise to the patient specific exploration of Aortic Dissections via a multi-scale and compliant model, harnessing imaging, computational fluid-dynamics (CFD) and dynamic boundary conditions. Results relating to the first workflow include some core outputs of the multiporoelastic modelling framework, and the representation of peri-arterial swelling and peri-venous drainage solution fields. The latter solution fields were statistically analysed for a cohort of thirty-five subjects (stratified with respect to disease status, gender and activity level). The second workflow allowed for a better understanding of complex aortic dissection cases utilising both a rigid-wall model informed by minimal and clinically common datasets as well as a moving-wall model informed by rich datasets.

[HaNDL syndrome in a 12-year-old girl]. / Sindrome HaNDL en una niña de 12 años.

INTRODUCTION: HaNDL (headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is a self-limiting benign condition which, as its name suggests, causes episodes of transient neurological deficits of a motor, sensory, aphasic and, less frequently, visual nature lasting several hours, accompanied or followed by moderate-to-severe headache and lymphocytosis of the cerebrospinal fluid. Its incidence is low in adulthood, and it is extremely uncommon in the paediatric age. Recurrence of episodes usually occurs in the first three months. It has an excellent prognosis. CASE REPORT: A 12-year-old female with intense frontal headache that suddenly begins on the tenth day, with clinical signs and symptoms of dysarthria and right hemiparesis with subsequent aphasia and generalised hypotonia. After ruling out other conditions by means of complementary examinations and the clinical course, the patient was finally diagnosed with HaNDL syndrome, since it fulfilled the clinical criteria of the International Headache Society (IHS). CONCLUSIONS: The patient met the criteria established by the IHS for the diagnosis of HaNDL syndrome. The main historical, epidemiological and clinical data are analysed and the differential diagnosis of HaNDL syndrome in the paediatric age is described.

TITLE: Sindrome HaNDL en una niña de 12 años.Introduccion. El sindrome HaNDL (headache and neurologic deficits with cerebrospinal fluid lymphocytosis) es una entidad autolimitada y benigna que cursa, como su nombre indica, con aparicion de episodios de deficits neurologicos transitorios de naturaleza motora, sensitiva o afasica, y menos frecuentemente visual, de varias horas de duracion, acompañados o seguidos de cefalea moderada-grave y linfocitosis del liquido cefalorraquideo. Su incidencia es baja en la edad adulta, y casi excepcional en la edad pediatrica. La recurrencia de los episodios suele producirse en los primeros tres meses. El pronostico es excelente. Caso clinico. Mujer de 12 años con cefalea frontal intensa que inicia en el decimo dia, de forma brusca, clinica de disartria y hemiparesia derecha con posterior afasia e hipotonia generalizada. Tras descartarse mediante exploraciones complementarias y evolucion clinica otras entidades, fue finalmente diagnosticada de sindrome HaNDL, ya que cumplia los criterios clinicos de la Sociedad Internacional de Cefaleas (IHS). Conclusiones. La paciente reunio los criterios de la IHS para el diagnostico de sindrome HaNDL. Se analizan los principales datos historicos, epidemiologicos y clinicos, y se expone el diagnostico diferencial del sindrome HaNDL en la edad pediatrica.