Natural course of septo-optic dysplasia: Retrospective analysis of 20 cases

Introducción. La displasia septoóptica (DSO) es la combinación variable de signos de disgenesia de línea media cerebral, hipoplasia de nervios ópticos y disfunción hipotálamo-hipofisaria, asociándose, a veces, con un espectro variado de malformaciones de la corteza cerebral. Objetivo. Describir la evolución natural y los hallazgos de neuroimagen en una serie de 20 pacientes diagnosticados. Pacientes y métodos. Se revisan de forma retrospectiva las características epidemiológicas, clínicas y neurroradiológicas de 20 pacientes consecutivos diagnosticados de DSO entre enero de 1985 y enero de 2010. Se analizaron los datos de tomografía computarizada, resonancia magnética craneal, electroencefalograma, potenciales evocados visuales, valoración oftalmológica, cariotipo y estudio endocrinológico. En siete pacientes, se realizó estudio del gen Homeobox HESX1. Resultados. El 60% de los casos presentaba antecedentes patológicos en el primer trimestre de gestación, con las ecografías fetales normales. Clínicamente, destacaban manifestaciones visuales (85%), alteraciones endocrinas (50%), retraso mental (60%) y crisis epilépticas (55%). Un 55% se asociaba a anomalías de migración neuronal. En un 45%, la DSO era el único hallazgo de neuroimagen. Se realizó cariotipo a todos, siendo normal. El gen HESX1 fue positivo en dos de los siete casos estudiados (ambos con DSO aislada). Ninguno con mutación en el gen HESX1 presentaba consanguinidad familiar. No se realizó estudio genético a los padres. Conclusiones. La DSO debe clasificarse como un síndrome malformativo heterogéneo, que asocia múltiples anomalías cerebrales, oculares, endocrinas y sistémicas. Las formas más graves se asocian con anomalías de la migración neuronal y de la organización cortical (AU)Introduction. Septo-optic dysplasia (SOD) is the variable combination of signs of dysgenesis of the midline of the brain, hypoplasia of the optic nerves and hypothalamus-pituitary dysfunction, which is sometimes associated with a varied spectrum of malformations of the cerebral cortex. Aims. To describe the natural history and neuroimaging findings in a series of 20 diagnosed patients. Patients and methods. We review the epidemiological, clinical and neuroimaging characteristics of 20 consecutive patients diagnosed with SOD between January 1985 and January 2010. Data obtained from computerised tomography, magnetic resonance imaging of the head, electroencephalogram, visual evoked potentials, ophthalmological evaluation, karyotyping and endocrinological studies were analysed. In seven patients, a study of the gene Homeobox HESX1 was conducted. Results. Pathological antecedents in the first three months of gestation were presented by 60% of the cases, with normal results in the foetal ultrasound scans. Clinically, the most striking features were visual manifestations (85%), endocrine disorders (50%), mental retardation (60%) and epileptic seizures (55%). Fifty-five per cent were associated to abnormal neuronal migration. In 45%, SOD was the only finding in the neuroimaging scans. Karyotyping was performed in all cases, the results being normal. Gene HESX1 was positive in two of the seven cases studied (both with isolated SOD). None of those with mutation in gene HESX1 presented familial consanguinity. No gene study was conducted with the parents. Conclusions. SOD must be classified as a heterogeneous malformation syndrome, which is associated to multiple brain, ocular, endocrine and systemic anomalies. The most severe forms are associated with abnormal neuronal migration and cortical organisation (AU

Management and conservation of fish populations in mountain streams: An holistic approach in the framework of LIFE DIVAQUA project

Producción CientíficaThe recovery of threatened and endangered fish species is among the highest priorities for biodiversity conservation in national parks and fisheries management in nearby areas. Threats to fish populations are numerous and include habitat fragmentation and degradation, proliferation of invasive and pathogen species, and climate change. Moreover, mountain areas often share the most critical threats. However, there does not exist a common strategy that integrates conservation and management plans for fish populations in mountain areas. In this regard, LIFE DIVAQUA designed a conservation strategy that integrates new knowledge gained from scientific research and long-term monitoring data, and considers the main threats to fish populations in mountain areas: (1) A long term monitoring program has been already implemented for 10 years, revealing temporal trends of fish populations in mountain streams. (2) Modeling of fish population by the use of environmental DNA allowed analyzing fish distributions in areas with scarce data and evaluating habitat suitability maps. (3) Fishways construction and removal of river barriers substantially increased the distribution area of endangered species. (4) The analysis of climate change effects in water temperature and hydrology led to the implementation of environmental flows under a climate change scenario; (5) Monitoring fish diseases, their occurrence, and temporal changes (e.g., Aeromonas spp.) can be used as an early warning signal of ecosystem unbalance. A pilot study for the implementation of this conservation and management plan in the LIFE DIVAQUA project is showing promising results. However, the success of conservation and management strategies requires a broader approach. This includes the participation of a wide range of partners and stakeholders and utilizes independent scientific oversight, assessment, and project adjustments to ensure conservation goals are met.Comisión Europea - (grant LIFE18 NAT/ES/000121

Myofascial Trigger Points, Pain, Disability, and Sleep Quality in Patients with Chronic Nonspecific Low Back Pain

[EN] Objective: To investigate the difference in the presence of trigger points (TrPs) between patients with chronic nonspecific low back pain (LBP) and healthy people, and to determine the relationship of TrPs with the intensity of ongoing pain, disability, and sleep quality. Design: A cross-sectional study. Setting: The role of TrPs in LBP has not been determined. Patients: Forty-two patients with nonspecific LBP (50% women), aged 23-55 years old, and 42 age- and sex-matched controls participated. Outcome measures: TrPs were bilaterally explored within the quadratus lumborum, iliocostalis lumborum, psoas, piriformis, gluteus minimus, and gluteus medius muscles in a blinded design. TrPs were considered active if the subject recognized the local and referred pain as familiar symptoms, and TrPs were considered latent if the pain was not recognized as a familiar symptom. Pain measures were collected with a numerical pain rate scale, disability was assessed with the Roland-Morris questionnaire, and sleep quality was determined with the Pittsburgh Sleep Quality Index. Results: Patients with nonspecific LBP exhibited a greater disability and worse sleep quality than healthy controls (P < 0.001). Patients with nonspecific LBP exhibited a mean of 3.5 ± 2.3 active TrPs. Further, patients with nonspecific LBP showed a greater (P < 0.001) number of latent TrPs (mean: 2.0 ± 1.5) than healthy controls (mean: 1.0 ± 1.5). Active TrPs in the quadratus lumborum, iliocostalis lumborum, and gluteus medius muscles were the most prevalent in patients with nonspecific LBP. A greater number of active TrPs was associated with higher pain intensity (rs = 0.602; P < 0.001) and worse sleep quality (rs = 0.338; P = 0.03). Conclusions: The local and referred pain elicited by active TrPs in the back and hip muscles contributes to pain symptoms in nonspecific LBP. Patients had higher disability and worse sleep quality than controls. The number of active TrPs was associated with pain intensity and sleep quality. It is possible that a complex interaction among these factors is present in patients with nonspecific LBP

Metabolic polygenic risk scores effect on antipsychotic-induced metabolic dysregulation: A longitudinal study in a first episode psychosis cohort

[EN] Objective: Metabolic syndrome is a health-threatening condition suffered by approximately one third of schizophrenia patients and largely attributed to antipsychotic medication. Previous evidence reports a common genetic background of psychotic and metabolic disorders. In this study, we aimed to assess the role of polygenic risk scores (PRSs) on the progression of the metabolic profile in a first-episode psychosis (FEP) cohort. Method: Of the 231 FEP individuals included in the study, 192-220 participants were included in basal analysis and 118-179 in longitudinal 6-month models. Eleven psychopathologic and metabolic PRSs were constructed. Basal and longitudinal PRSs association with metabolic measurements was assessed by statistical analyses.Results: No major association of psychopathological PRSs with the metabolic progression was found. However, high risk individuals for depression and cholesterol-related PRSs reported a higher increase of cholesterol levels during the follow-up (FDR <= 0.023 for all analyses). Their effect was comparable to other well-established pharmacological and environmental risk factors (explaining at least 1.2% of total variance).Conclusion: Our findings provide new evidence of the effects of metabolic genetic risk on the development of metabolic dysregulation. The future establishment of genetic profiling tools in clinical procedures could enable practitioners to better personalize antipsychotic treatment selection and dosage

A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood.

Little is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy. © Copyright © 2021 Jantus-Lewintre, Massutí Sureda, González Larriba, Rodríguez-Abreu, Juan, Blasco, Dómine, Provencio Pulla, Garde, Álvarez, Maestu, Pérez de Carrión, Artal, Rolfo, de Castro, Guillot, Oramas, de las Peñas, Ferrera, Martínez, Serra, Rosell and Camps

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages

Mapping the temporary and perennial character of whole river networks

Knowledge of the spatial distribution of temporary and perennial river channels in a whole catchment is important for effective integrated basin management and river biodiversity conservation. However, this information is usually not available or is incomplete. In this study, we present a statistically based methodology to classify river segments from a whole river network (Deva-Cares catchment, Northern Spain) as temporary or perennial. This method is based on an a priori classification of a subset of river segments as temporary or perennial, using field surveys and aerial images, and then running Random Forest models to predict classification membership for the rest of the river network. The independent variables and the river network were derived following a computer-based geospatial simulation of riverine landscapes. The model results show high values of overall accuracy, sensitivity, and specificity for the evaluation of the fitted model to the training and testing data set (?0.9). The most important independent variables were catchment area, area occupied by broadleaf forest, minimum monthly precipitation in August, and average catchment elevation. The final map shows 7525 temporary river segments (1012.5 km) and 3731 perennial river segments (662.5 km). A subsequent validation of the mapping results using River Habitat Survey data and expert knowledge supported the validity of the proposed maps. We conclude that the proposed methodology is a valid method for mapping the limits of flow permanence that could substantially increase our understanding of the spatial links between terrestrial and aquatic interfaces, improving the research, management, and conservation of river biodiversity and functioning.We would like to thank the Journal Editor and the three referees for their comments and suggestions, which have greatly improved the manuscript. This study was partly funded by the Spanish Ministry of Economy and Competitiveness as part of the RIVERLANDS (Ref: BIA-2012–33572) and HYDRA (Ref: BIA-2015–71197) projects. Alexia María González-Ferreras is supported by a predoctoral research grant (Ref: BES-2013–065770) from the Spanish Ministry of Economy and Competitiveness, and José Barquín was supported by a Ramon y Cajal grant (Ref: RYC-2011–08313) from the Spanish Ministry of Economy and Competitiveness. We would like to thank the Government of Cantabria, the Principado de Asturias and the forest guards of the study areas for providing useful information. We would also like to acknowledge the Interautonomic Consortium of the Picos de Europa National Park and the Biodiversity Foundation from the Ministry of Agriculture, Food and Environment, for their advice and project support. Finally, we would also like to thank all the people involved in the field data collection, and those who read an early draft of the manuscript and suggested several improvements. The data and the data sources used in this study are cited and explained in the text. Readers can obtain further information about the data supporting the analysis and conclusions by contacting the corresponding author