Galaxies in voids assemble their stars slowly.

Galaxies in the Universe are distributed in a web-like structure characterized by different large-scale environments: dense clusters, elongated filaments, sheetlike walls and under-dense regions, called voids1-5. The low density in voids is expected to affect the properties of their galaxies. Indeed, previous studies6-14 have shown that galaxies in voids are, on average, bluer and less massive, and have later morphologies and higher current star formation rates than galaxies in denser large-scale environments. However, it has never been observationally proved that the star formation histories (SFHs) in voids are substantially different from those in filaments, walls and clusters. Here we show that void galaxies have had, on average, slower SFHs than galaxies in denser large-scale environments. We also find two main SFH types present in all the environments: 'short-timescale' galaxies are not affected by their large-scale environment at early times but only later in their lives; 'long-timescale' galaxies have been continuously affected by their environment and stellar mass. Both types have evolved more slowly in voids than in filaments, walls and clusters.

Implementation of pure shift 1 H NMR in metabolic phenotyping for structural information recovery of biofluid metabolites with complex spin systems.

NMR spectroscopy is a mainstay of metabolic profiling approaches to investigation of physiological and pathological processes. The one-dimensional proton pulse sequences typically used in phenotyping large numbers of samples generate spectra that are rich in information but where metabolite identification is often compromised by peak overlap. Recently developed pure shift (PS) NMR spectroscopy, where all J-coupling multiplicities are removed from the spectra, has the potential to simplify the complex proton NMR spectra that arise from biosamples and hence to aid metabolite identification. Here we have evaluated two complementary approaches to spectral simplification: the HOBS (band-selective with real-time acquisition) and the PSYCHE (broadband with pseudo-2D interferogram acquisition) pulse sequences. We compare their relative sensitivities and robustness for deconvolving both urine and serum matrices. Both methods improve resolution of resonances ranging from doublets, triplets and quartets to more complex signals such as doublets of doublets and multiplets in highly overcrowded spectral regions. HOBS is the more sensitive method and takes less time to acquire in comparison with PSYCHE, but can introduce unavoidable artefacts from metabolites with strong couplings, whereas PSYCHE is more adaptable to these types of spin system, although at the expense of sensitivity. Both methods are robust and easy to implement. We also demonstrate that strong coupling artefacts contain latent connectivity information that can be used to enhance metabolite identification. Metabolite identification is a bottleneck in metabolic profiling studies. In the case of NMR, PS experiments can be included in metabolite identification workflows, providing additional capability for biomarker discovery.

The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage.

BACKGROUND: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality. METHODS: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders. RESULTS: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks. CONCLUSIONS: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

Cyber sexual harassment against women and impact on health. A cross-sectional study in a representative population sample.

BACKGROUND: This study focuses on the frequency of cyber sexual harassment (CSH) and examines its link with five health impact indicators (self-perceived health, medication, suicidal ideation, suicide attempts and use of health services). METHODS: Analyzing the data provided by the 2019 Macro-survey on violence against women in Spain, two items of which refer to CSH. It was conducted in Spain on a representative sample of 9568 women aged over 16 years old. RESULTS: A total of 9.15% of the women surveyed had experienced CSH at some point in their lives. Being under 25 years old, having higher education, not being in a relationship, having no religious beliefs and having a certified disability are sociodemographic characteristics associated with a higher risk of CSH. Women who have experienced other forms of gender-based violence also show an increased risk. Female victims of CSH reported higher rates of suicidal ideation (20% versus 9.79% in non-victims of CSH) and suicidal attempts (7.20% versus 1.74% in non-victims of CSH). CONCLUSIONS: These findings have significant implications for the design of preventive health polices, which should incorporate strategies to address CSH as part of the continuum of multiple interrelated forms of gender violence that affect women and girls throughout their lives.

Systematic review of healthcare interventions for reducing gender-based violence impact on the mental health of women with disabilities.

PURPOSE: Women with disabilities are more exposed to violence. The health sector has a key role in all three levels of prevention of violence against women. The objective of this paper was to review the interventions for preventing gender-based violence and reducing its impact on the mental health of women with any form of disability. METHOD: Relevant studies were identified through conducting searches in PubMed, Scopus, CINAHL, PsyInfo, Social Services Abstracts, and PILOTS. Two reviewers analyzed and selected studies. A qualitative synthesis was made. RESULTS: 3149 references were obtained, among which eight articles describing nine interventions from the USA and the UK. Most were intended for women with mental/intellectual disability and assessed intimate partner or sexual violence. Only one study showed high methodological quality. They were found to be particularly effective as regards improvement of the skills acquired by participants, but the results as regards improved mental health are not consistent. CONCLUSION: Our review shows very little evidence of effective interventions. Further studies are required with higher internal validity and female sample groups with diverse disabilities. CLINICAL RELEVANCE: Gender-based violence is a highly prevalent problem for women with disabilities, and in addition to being a public health challenge is a violation of human rights. Health care systems and policymakers should take a key role in all three levels of prevention of violence against women with disabilities. Interventions with longer follow-up times are required. It is also important for interventions to be designed in consultation with people with disabilities.

Exploring the Integrated Role of miRNAs and lncRNAs in Regulating the Transcriptional Response to Amino Acids and Insulin-like Growth Factor 1 in Gilthead Sea Bream (Sparus aurata) Myoblasts.

In this study, gilthead sea bream (Sparus aurata) fast muscle myoblasts were stimulated with two pro-growth treatments, amino acids (AA) and insulin-like growth factor 1 (Igf-1), to analyze the transcriptional response of mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and to explore their possible regulatory network using bioinformatic approaches. AA had a higher impact on transcription (1795 mRNAs changed) compared to Igf-1 (385 mRNAs changed). Both treatments stimulated the transcription of mRNAs related to muscle differentiation (GO:0042692) and sarcomere (GO:0030017), while AA strongly stimulated DNA replication and cell division (GO:0007049). Both pro-growth treatments altered the transcription of over 100 miRNAs, including muscle-specific miRNAs (myomiRs), such as miR-133a/b, miR-206, miR-499, miR-1, and miR-27a. Among 111 detected lncRNAs (>1 FPKM), only 30 were significantly changed by AA and 11 by Igf-1. Eight lncRNAs exhibited strong negative correlations with several mRNAs, suggesting a possible regulation, while 30 lncRNAs showed strong correlations and interactions with several miRNAs, suggesting a role as sponges. This work is the first step in the identification of the ncRNAs network controlling muscle development and growth in gilthead sea bream, pointing out potential regulatory mechanisms in response to pro-growth signals.

The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review.

This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches.

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Diversification linked to larval host plant in the butterfly Eumedonia eumedon.

It is widely accepted that the relationship between phytophagous insects and their host plants influences insect diversification. However, studies addressed at documenting host-associated genetic differentiation (HAD) and the mechanisms that drive reproductive isolation in host-associated lineages (or host races) are still scarce relative to insect diversity. To uncover further evidence on the HAD processes in Lepidoptera, we investigated the genetic structure of the geranium argus butterfly (Eumedonia eumedon) and tested for isolation by ecology (IBE) vs. isolation by distance (IBD). Genomic data revealed an array of host races (three of them in the same mountain range, the Cantabrian Mountains, northern Iberia) at apparently distinct levels of reproductive isolation. We found a pattern of IBE mediated by HAD at both local and European scales, in which genetic differentiation between populations and individuals correlated significantly with the taxonomic relatedness of the host plants. IBD was significant only when considered at the wider European scale. We hypothesize that, locally, HAD between Geranium-feeding populations was caused (at least partially) by allochrony, that is via adaptation of adult flight time to the flowering period of each host plant species. Nevertheless, the potential reproductive isolation between populations using Erodium and populations using Geranium cannot be explained by allochrony or IBD, and other mechanisms are expected to be at play.

Risk factors and outcome of epilepsy in adults with cerebral palsy or intellectual disability.

INTRODUCTION: Epilepsy is found in 10-60% of individuals with cerebral palsy (CP) and 5.5-35% with intellectual disability (ID). However, little is known about the long-term evolution of epilepsy among adults. The aim of the study is to describe the factors associated with epilepsy and its outcome in a population of adults with CP or ID. METHODS: This retrospective study reviewed the medical records of 306 individuals with CP/ID. All individuals underwent neurological, psychiatric, and neuropsychological follow-ups. RESULTS: In the cohort, 72.5% of the individuals had a CP diagnosis, with a mean age of 36.4 years (IQR 24.0-46.0). Epilepsy was present in 55.6% of the individuals and was associated with CP (p < 0.01), spastic subtype (p < 0.01), a higher degree of ID (p < 0.01), hemorrhagic and congenital malformation etiologies (p 0.011), abnormal neuroimaging (p < 0.01), and worse scores on motor and communication scales (p < 0.01). Drug-resistant epilepsy (DRE) (22.4%) was associated with higher scores on motor scales (p < 0.01). Additionally, 42.3% of the individuals who attempted antiseizure medication (ASM) withdrawal experienced recurrence, which was associated with epileptic activity on the electroencephalogram (EEG) (p 0.004). CONCLUSIONS: Epilepsy is a common comorbidity in adults with CP or ID and is associated with greater brain damage and a more severe phenotype. Seizure recurrence after ASM withdrawal occurred in half of the individuals and was associated with epileptic activity on the EEG.

Factors associated with migraine aura mimicking stroke in code stroke.

INTRODUCTION: Migraine with aura (MA) is a frequent stroke simulator that can lead to erroneous diagnosis and subsequent unnecessary acute or secondary prevention treatments. We analyzed clinical and laboratory data of migraine with aura and ischemic stroke patients to detect differences that could help in the diagnosis. METHODS: Retrospective analysis of a consecutive register of code strokes between January 2005 and June 2020. Diagnosis of ischemic stroke or MA was collected. Multivariable logistic regression analyses were performed to test associations between clinical and blood data with ischemic stroke. RESULTS: Of 3140 code strokes, 2424 (77.2%) were ischemic strokes and 34 (1.1%) were MA. Migraine cases were younger, more frequently females and with lower prevalence of vascular risk factors. Initial NIHSS was lower in MA cases, but no differences were seen in fibrinolysis rate (30%). Blood test showed lower levels of glucose, D-dimer, and fibrinogen in MA cases. Multivariable model showed and independent association for ischemic stroke with age [OR, (95%CI): 1.09, (1.07-1.12, p < 0.001], male sex [OR, (95%CI): 4.47, (3.80-5.13), p < 0.001], initial NIHSS [OR, (95%CI): 1.21, (1.07-1.34), p < 0.01], and fibrinogen levels [OR, (95%CI): 1.01, (1.00-1.01), p < 0.05]. A model including sex male OR: 3.55 [2.882; 4.598], p < 0.001, and cutoff points (age > 65, OR: 7.953 [7.256; 8.649], p < 0.001, NIHSS > 6, OR: 3.740 [2.882; 4.598], p < 0.01, and fibrinogen > 400 mg/dL, OR: 2.988 [2.290; 3.686], p < 0.01) showed a good global discrimination capability AUC = 0.89 (95%CI: 0.88-0.94). CONCLUSIONS: In code stroke, a model including age, sex, NIHSS, and fibrinogen showed a good discrimination capability to differentiate between MA and Ischemic stroke. Whether these variables can be implemented in a diagnostic rule should be tested in future studies.

Spatial distribution of unscheduled hospital admissions for chronic obstructive pulmonary disease in the central area of Asturias, Spain.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major causes of mortality worldwide and also reports high morbidity rates and the global burden COPD has continued to rise over the last several decades. The best-known COPD risk factors are tobacco smoke and air pollution, but genetics, age, sex, and socioeconomic status are additional factors. This study aimed to assess the spatial distribution of unscheduled COPD hospital admissions of men and women in the central area of Asturias during 2016-2018 and identify trends, spatial patterns, or clusters in the area. METHODS: Unscheduled COPD hospital admissions in the central area of Asturias were registered, geocoded, and grouped by census tracts (CTs), age, and sex. Standardized admission ratio, smoothed relative risk, posterior risk probability, and spatial clusters between relative risks throughout the study area were calculated and mapped. RESULTS: The spatial distribution of COPD hospital admissions differed between men and women. For men, high-risk values were located primarily in the northwestern area of the study, whereas for women the cluster pattern was not as clear and high-risk CTs also reached central and southern areas. In both men and women, the north-northwest area included the majority of CTs with high-risk values. CONCLUSIONS: The present study showed the existence of a spatial distribution pattern of unscheduled COPD hospital admissions in the central area of Asturias that was more pronounced for men than for women. This study could provide a starting point for generating knowledge about COPD epidemiology in Asturias.

Spatial distribution of hospital admissions for asthma in the central area of Asturias, Northern Spain.

BACKGROUND: Asturias is one of the communities with the highest rates of hospital admission for asthma in Spain. The environmental pollution or people lifestyle are some of the factors that contribute to the appearance or aggravation of this illness. The aim of this study was to show the spatial distribution of asthma admissions risks in the central municipalities of Asturias and to analyze the observed spatial patterns. METHODS: Urgent hospital admissions for asthma and status asthmaticus occurred between 2016 to 2018 on the public hospitals of the central area of Asturias were used. Population data were assigned in 5 age groups. Standardised admission ratio (SAR), smoothed relative risk (SRR) and posterior risk probability (PP) were calculated for each census tract (CT). A spatial trend analysis was run, a spatial autocorrelation index (Morans I) was calculated and a cluster and outlier analysis (Anselin Local Morans I) was finally performed in order to analyze spatial clusters. RESULTS: The total number of hospital urgent asthma admissions during the study period was 2324, 1475 (63.46%) men and 849 (36.56%) women. The municipalities with the highest values of SRR and PP were located on the northwest area: Avilés, Gozón, Carreño, Corvera de Asturias, Castrillón and Illas. A high risk cluster was found for the municipalities of Avilés, Gozón y Corvera de Asturias. CONCLUSIONS: The spatial analysis showed high risk of hospitalization for asthma on the municipalities of the northwest area of the study, which highlight the existence of spatial inequalities on the distribution of urgent hospital admissions.

Machine Learning Approximations to Predict Epigenetic Age Acceleration in Stroke Patients.

Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A. We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, and target organ damage. We estimated Age-A using Hannum's epigenetic clock, and trained six different models to predict Age-A: a conventional linear regression model, four ML models (elastic net regression (EN), K-Nearest neighbors, random forest, and support vector machine models), and one deep learning approximation (multilayer perceptron (MLP) model). The best-performing models were EN and MLP; although, the predictive capability was modest (R2 0.358 and 0.378, respectively). In conclusion, our results support the influence of these factors on Age-A; although, they were not enough to explain most of its variability.

Increased COVID-19 Mortality in People With Previous Cerebrovascular Disease: A Population-Based Cohort Study.

BACKGROUND: The aim of the study was to determine the association between previous stroke and mortality after coronavirus disease 2019 (COVID-19) according to sex, age groups, and stroke subtypes. METHODS: Prospective population-based cohort study including all COVID-19 positive cases between February 1 and July 31, 2020. Comorbidities and mortality were extracted using linked health administration databases. Previous stroke included transient ischemic attack, ischemic stroke, hemorrhagic stroke, spontaneous subarachnoid hemorrhage, and combined stroke for cases with more than one category. Other comorbidities were obesity, diabetes, hypertension, ischemic heart disease, atrial fibrillation, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, cirrhosis, dementia, individual socioeconomic index, and deprivation index. Cases were followed up until December 31, 2020. Primary outcome was mortality of any cause after COVID-19 positivity. Cox proportional regression analysis adjusted for comorbidities was used. Stratified analyses were performed for sex and age (<60, 60-79, and ≥80 years). RESULTS: There were 91 629 COVID-19 cases. Previous strokes were 5752 (6.27%), of which 3887 (67.57%) were ischemic, 1237 (21.50%) transient ischemic attack, 255 (4.43%) combined, 203 (3.53%) hemorrhagic, and 170 (2.96%) subarachnoid hemorrhage. There were 9512 deaths (10.38%). Mortality was associated with previous stroke (hazard ratio [HR]=1.12 [95% CI, 1.06-1.18]; P<0.001), in both sexes separately (men=1.13 [1.05-1.22]; P=0.001; women=1.09 [1.01-1.18]; P=0.023), in people <60 years (HR=2.97 [1.97-4.48]; P<0.001) and 60 to 79 years (HR=1.32 [1.19-1.48]; P<0.001) but not in people ≥80 years (HR=1.02 [0.96-1.09]; P=0.437). Ischemic (HR=1.11 [1.05-1.18]; P=0.001), hemorrhagic (HR=1.53 [1.20-1.96]; P=0.001) and combined (HR=1.31 [1.05-1.63]; P=0.016) strokes were associated but not transient ischemic attack. Subarachnoid hemorrhage was associated only in people <60 years (HR=5.73 [1.82-18.06]; P=0.003). CONCLUSIONS: Previous stroke was associated with a higher mortality in people younger than 80 years. The association occurred for both ischemic and hemorrhagic stroke but not for transient ischemic attack. These data might help healthcare authorities to establish prioritization strategies for COVID-19 vaccination.

Familial Mediterranean fever in the pediatric population.

Familial Mediterranean fever (FMF) is the most frequent autoinflammatory disorder characterized by short, repeated, and self-limiting crises of fever and serositis. The disease was described as autosomal recessive hereditary transmission secondary to variants of the MEFV (MEditerranean FeVer) gene, even though a variable proportion of patients only present a heterozygous variant. FMF is very common in certain ethnic groups (Turkish, Armenian, Arab, and Jewish), even though it has been described throughout the Mediterranean and elsewhere in the world. The clinical manifestations are variable, with secondary amyloidosis being the most serious complication of the disorder. Treatment and prophylaxis are mainly based on the administration of colchicine, which prevents the crises and avoids complications in most cases. This study reviews the course of seven pediatric patients diagnosed with FMF during the period 2010-2018 at a district hospital. Most of the patients were of Caucasian origin, with onset at an early age in the form of fever as the main symptom, and some patients moreover presented less frequent manifestations (pericardial effusion, sensorineural hearing loss). Two cases presented plasmatic amyloid A protein elevation that subsided with the treatment. All the patients initially received colchicine, and one of them required prescription of anakinra, which was replaced by canakinumab due to a serious adverse reaction. There were no cases of consanguinity, and all the patients were of Mediterranean origin. The subjects showed a favorable course over the years, which was attributed to the early diagnosis and treatment provided.

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.

Myomaker and Myomixer Characterization in Gilthead Sea Bream under Different Myogenesis Conditions.

Skeletal muscle is formed by multinucleated myofibers originated by waves of hyperplasia and hypertrophy during myogenesis. Tissue damage triggers a regeneration process including new myogenesis and muscular remodeling. During myogenesis, the fusion of myoblasts is a key step that requires different genes' expression, including the fusogens myomaker and myomixer. The present work aimed to characterize these proteins in gilthead sea bream and their possible role in in vitro myogenesis, at different fish ages and during muscle regeneration after induced tissue injury. Myomaker is a transmembrane protein highly conserved among vertebrates, whereas Myomixer is a micropeptide that is moderately conserved. myomaker expression is restricted to skeletal muscle, while the expression of myomixer is more ubiquitous. In primary myocytes culture, myomaker and myomixer expression peaked at day 6 and day 8, respectively. During regeneration, the expression of both fusogens and all the myogenic regulatory factors showed a peak after 16 days post-injury. Moreover, myomaker and myomixer were present at different ages, but in fingerlings there were significantly higher transcript levels than in juveniles or adult fish. Overall, Myomaker and Myomixer are valuable markers of muscle growth that together with other regulatory molecules can provide a deeper understanding of myogenesis regulation in fish.

Gender-based differences in perceptions about sexual violence, equality and drug­facilitated sexual assaults in nightlife contexts. / Diferencias de género en percepciones sobre violencia sexual, igualdad y agresiones sexuales facilitadas por drogas en ocio nocturno.

Sexual violence, including drug-facilitated sexual assaults, is a serious issue that is becoming increasingly common in leisure nightlife contexts. This study provides information about the attitudes and perceptions of Spanish youths towards sexual violence within that setting. The participants were recruited by a snowball sampling scheme. A bivariate analysis was performed to identify possible sociodemographic and nightlife recreational habit factors related to gender. The statistical significance of the differences between the studied variables was assessed using the chi-squared and Fisher's exact tests. Women perceived a low level of personal security, as well as the existence of social perceptions penalizing female more than male drug use, and blaming women for the sexual violence they suffer. Women also recognised less explicit violent behaviours as violence significantly more than men did. Men were more willing to have sexual intercourse with someone unable to express consent because of drugs. In addition, they believed more strongly that sexual assaults take place because of the victim's use of alcohol or other drugs. In a leisure nightlife context, women are prone to perceive a lack of social support for themselves and the feeling of impunity for the perpetrators. Furthermore, numerous misconceptions surround drug-facilitated sexual assaults, with the majority of respondents believing that assaults happen after the surreptitious administration of substances to the victim by an unknown assailant. Moreover, the involvement of alcohol was underestimated. Our findings are useful for designing prevention efforts, demystifying the drug-facilitated sexual assaults and enhancing social support for victims.

La violencia sexual, incluyendo las agresiones sexuales facilitadas por drogas, es un serio problema cada vez más común en los contextos de ocio nocturno. Este trabajo estudia las actitudes y percepciones de la juventud española en torno a la violencia sexual en dicho ámbito. Los participantes se reclutaron mediante muestreo en bola de nieve. Se realizó un análisis bivariado para identificar posibles factores sociodemográficos y de ocio nocturno relacionados con género. La significación estadística de las diferencias entre estas variables se evaluó mediante las pruebas de chi-cuadrado y exacta de Fisher. Las mujeres percibieron un menor nivel de seguridad personal, así como la existencia de percepciones sociales que penalizan en mayor medida el consumo de drogas femenino que el masculino, y que culpabilizan a las mujeres por la violencia que sufren. Además, ellos mostraron mayor disposición a mantener relaciones sexuales con personas incapaces de otorgar su consentimiento debido a los efectos de las drogas. Los hombres creen en mayor medida que las agresiones sexuales ocurren debido al uso de alcohol u otras drogas por parte de las víctimas. En el contexto de ocio nocturno, las mujeres son propensas a percibir la existencia de una falta de apoyo social hacia ellas, así como un sentimiento de impunidad social hacia los agresores. Además, existen numerosas concepciones erróneas en torno a las agresiones sexuales facilitadas por drogas. La mayoría cree que las agresiones ocurren tras la administración encubierta de sustancias a la víctima por parte de un agresor desconocido. Además, se subestimó la participación del alcohol. Nuestros hallazgos son útiles para diseñar esfuerzos preventivos bien dirigidos, desmitificar el fenómeno de las agresiones sexuales facilitadas por drogas y mejorar el apoyo social a las víctimas.

ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology.

Sorafenib is a multikinase inhibitor widely used in cancer therapy with an antitumour effect related to biological processes as proliferation, migration or invasion, among others. Initially designed as a Raf inhibitor, Sorafenib was later shown to also block key molecules in tumour progression such as VEGFR and PDGFR. In addition, sorafenib has been connected with key signalling pathways in cancer such as EGFR/EGF. However, no definitive clue about the molecular mechanism linking sorafenib and EGF signalling pathway has been established so far. Our data in HeLa, U2OS, A549 and HEK293T cells, based on in silico, chemical and genetic approaches demonstrate that the MEK5/ERK5 signalling pathway is a novel target of sorafenib. In addition, our data show how sorafenib is able to block MEK5-dependent phosphorylation of ERK5 in the Ser218/Tyr220, affecting the transcriptional activation associated with ERK5. Moreover, we demonstrate that some of the effects of this kinase inhibitor onto EGF biological responses, such as progression through cell cycle or migration, are mediated through the effect exerted onto ERK5 signalling pathway. Therefore, our observations describe a novel target of sorafenib, the ERK5 signalling pathway, and establish new mechanistic insights for the antitumour effect of this multikinase inhibitor.