Face mask use during the COVID-19 pandemic: how risk perception, experience with COVID-19, and attitude towards government interact with country-wide policy stringency.

BACKGROUND: During the 2020 COVID-19 pandemic, governments imposed numerous regulations to protect public health, particularly the (mandatory) use of face masks. However, the appropriateness and effectiveness of face mask regulations have been widely discussed, as is apparent from the divergent measures taken across and within countries over time, including mandating, recommending, and discouraging their use. In this study, we analyse how country-level policy stringency and individual-level predictors associate with face mask use during the early stages of the global COVID-19 pandemic. METHOD: First, we study how (self and other-related) risk perception, (direct and indirect) experience with COVID-19, attitude towards government and policy stringency shape face mask use. Second, we study whether there is an interaction between policy stringency and the individual-level variables. We conduct multilevel analyses exploiting variation in face mask regulations across countries and using data from approximately 7000 students collected in the beginning of the pandemic (weeks 17 through 19, 2020). RESULTS: We show that policy stringency is strongly positively associated with face mask use. We find a positive association between self-related risk perception and mask use, but no relationship of mask use with experience with COVID-19 and attitudes towards government. However, in the interaction analyses, we find that government trust and perceived clarity of communication moderate the link between stringency and mask use, with positive government perceptions relating to higher use in countries with regulations and to lower use in countries without regulations. CONCLUSIONS: We highlight that those countries that aim for widespread use of face masks should set strict measures, stress self-related risks of COVID-19, and use clear communication.

Generation of the First Human In Vitro Model for McArdle Disease Based on iPSC Technology.

McArdle disease is a rare autosomal recessive disorder caused by mutations in the PYGM gene. This gene encodes for the skeletal muscle isoform of glycogen phosphorylase (myophosphorylase), the first enzyme in glycogenolysis. Patients with this disorder are unable to obtain energy from their glycogen stored in skeletal muscle, prompting an exercise intolerance. Currently, there is no treatment for this disease, and the lack of suitable in vitro human models has prevented the search for therapies against it. In this article, we have established the first human iPSC-based model for McArdle disease. For the generation of this model, induced pluripotent stem cells (iPSCs) from a patient with McArdle disease (harbouring the homozygous mutation c.148C>T; p.R50* in the PYGM gene) were differentiated into myogenic cells able to contract spontaneously in the presence of motor neurons and generate calcium transients, a proof of their maturity and functionality. Additionally, an isogenic skeletal muscle model of McArdle disease was created. As a proof-of-concept, we have tested in this model the rescue of PYGM expression by two different read-through compounds (PTC124 and RTC13). The developed model will be very useful as a platform for testing drugs or compounds with potential pharmacological activity.

The relationship between the socio-economic gradient and cigarette consumption in Spain. / La relación entre el gradiente socioeconómico y el consumo de cigarrillos en España.

The objective of the study was to analyze the relationship between individual socioeconomic characteristics and cigarette consumption in Spain. The sample consisted of 19,931 individuals aged 15 or older who completed the European Health Interview Survey for Spain (EHSS-2014). Variables: prevalence and intensity of cigarette consumption. Multivariate ordered logistic regression analysis was performed with the following socioeconomic variables: social classes, educational attainment, main activity, economic situation and, for the working population, the activity sector. Other control variables were sociodemographic variables and healthy lifestyle habits (physical exercise, diet and alcohol consumption). The factors that relate to greater prevalence are: lower social class, not having university studies, being unemployed, having worse economic situation and working in hospitality industry. On the other hand, the variables related to higher intensity of cigarette consumption of the smoking population are: lower social class, not having university studies, and being neither a student nor on a permanent contract. Regarding control variables, those regressors associated with a higher prevalence and intensity of cigarette consumption are: being male, being aged between 36 and 65, being divorced, having fewer children at home and having worse lifestyle habits.

El objetivo del estudio fue analizar la relación entre las características socioeconómicas individuales y el consumo de cigarrillos en España. La muestra estaba formada por 19.931 individuos de 15 o más años de edad de la Encuesta Europea de Salud en España (EESE) de 2014. Variables: prevalencia y nivel de consumo. Se realizó análisis de regresión multivariante logística ordinal con las variables socioeconómicas clase social, nivel educativo, actividad principal, situación económica y sector de actividad (solo para población trabajadora). Otras variables de control incluidas fueron las características sociodemográficas y los hábitos de vida saludables (ejercicio físico, alimentación y consumo de alcohol). Los factores que se relacionan con mayor prevalencia en el consumo de cigarrillos son: inferior clase social, no tener estudios universitarios, ser desempleado, tener peor situación económica y trabajar en hostelería. Por su parte, las variables relacionadas con el nivel de consumo de la población fumadora son: inferior clase social, no tener estudios universitarios, y no ser estudiante ni trabajador indefinido. En cuanto a las variables de control, aquellos regresores asociados a mayor prevalencia y nivel de consumo son: sexo masculino, edad entre 36 y 65 años, ser divorciado, menor número de niños en el hogar y peores hábitos de vida.

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice.

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by the progressive and irreversible loss of vision. We previously found that intraperitoneal administration of Adalimumab, a monoclonal anti-TNFα antibody, slowed down retinal degeneration in the murine model of RP, the rd10 mice. The aims of this study were to improve its neuroprotective effect and to deepen understanding of the molecular mechanisms involved in this effect. We analyzed (i) the in vitro effect of Adalimumab on the TNFα-mediated cell death in retinal cells; (ii) the effect of a single intravitreal injection of Adalimumab on retinal degeneration in rd10 mice at postnatal day (P) 23. In vitro studies showed that TNFα induced caspase and poly ADP ribose polymerase (PARP) activation, downregulation of (kinase receptor-interacting protein 1) RIPK1 and upregulation of RIPK3 in retinal cells. Adalimumab reduced cell death probably through the inhibition of caspase 3 activation. In vivo studies suggested that PARP and NLRP3 inflammasome are mainly activated and to a lesser extent caspase-dependent mechanisms in rd10 retinas at P23. Necroptosis seems to be inhibited by the downregulation of RIPK1. Adalimumab prevented from retinal degeneration without affecting caspase -dependent mechanisms but decreasing PARP activation, microglia activation as well as NLRP3 inflammasome.

HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 ( retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice. A generalized down-regulation of HIF-1α and its downstream targets was detected in parallel with reactive gliosis, suggesting high oxygen levels during retinal degeneration. At postnatal d 18, DMOG treatment reduced photoreceptor cell death and glial activation. In summary, retinas of rd10 mice seem to be exposed to a hyperoxic environment even at early stages of degeneration. HIF-1α stabilization could have a temporal neuroprotective effect on photoreceptor cell survival, glial activation, and antioxidant response at early stages of RP.-Olivares-González, L., Martínez-Fernández de la Cámara, C., Hervás, D., Millán, J. M., Rodrigo, R. HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease.

The adenosine monophosphate activated kinase protein (AMPK) is an evolutionary-conserved protein important for cell survival and organismal longevity through the modulation of energy homeostasis. Several studies suggested that AMPK activation may improve energy metabolism and protein clearance in the brains of patients with vascular injury or neurodegenerative disease. However, in Huntington's disease (HD), AMPK may be activated in the striatum of HD mice at a late, post-symptomatic phase of the disease, and high-dose regiments of the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide may worsen neuropathological and behavioural phenotypes. Here, we revisited the role of AMPK in HD using models that recapitulate the early features of the disease, including Caenorhabditis elegans neuron dysfunction before cell death and mouse striatal cell vulnerability. Genetic and pharmacological manipulation of aak-2/AMPKα shows that AMPK activation protects C. elegans neurons from the dysfunction induced by human exon-1 huntingtin (Htt) expression, in a daf-16/forkhead box O-dependent manner. Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKα1. Furthermore, AMPK protection is active in the mouse brain as delivery of gain-of-function AMPK-γ1 to mouse striata slows down the neurodegenerative effects of mHtt. Collectively, these data highlight the importance of considering the dynamic of HD for assessing the therapeutic potential of stress-response targets in the disease. We postulate that AMPK activation is a compensatory response and valid approach for protecting dysfunctional and vulnerable neurons in HD.

Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina.

Inherited retinal degenerations affecting both rod and cone photoreceptors constitute one of the causes of incurable blindness in the developed world. Cyclic guanosine monophosphate (cGMP) is crucial in the phototransduction and, mutations in genes related to its metabolism are responsible for different retinal dystrophies. cGMP-degrading phosphodiesterase 6 (PDE6) mutations cause around 4-5% of the retinitis pigmentosa, a rare form of retinal degeneration. The aim of this study was to evaluate whether pharmacological PDE6 inhibition induced retinal degeneration in cone-enriched cultures of porcine retina similar to that found in murine models. PDE6 inhibition was induced in cone-enriched retinal explants from pigs by Zaprinast. PDE6 inhibition induced cGMP accumulation and triggered retinal degeneration, as determined by TUNEL assay. Western blot analysis and immunostaining indicated that degeneration was accompanied by caspase-3, calpain-2 activation and poly (ADP-ribose) accumulation. Oxidative stress markers, total antioxidant capacity, thiobarbituric acid reactive substances (TBARS) and nitric oxide measurements revealed the presence of oxidative damage. Elevated TNF-alpha and IL-6, as determined by enzyme immunoassay, were also found in cone-enriched retinal explants treated with Zaprinast. Our study suggests that this ex vivo model of retinal degeneration in porcine retina could be an alternative model for therapeutic research into the mechanisms of photoreceptor death in cone-related diseases, thus replacing or reducing animal experiments.

PCR-Based Strategy for Introducing CRISPR/Cas9 Machinery into Hematopoietic Cell Lines.

Acute myeloid leukemia is a complex heterogeneous disease characterized by the clonal expansion of undifferentiated myeloid precursors. Due to the difficulty in the transfection of blood cells, several hematological models have recently been developed with CRISPR/Cas9, using viral vectors. In this study, we developed an alternative strategy in order to generate CRISPR constructs by fusion PCR, which any lab equipped with basic equipment can implement. Our PCR-generated constructs were easily introduced into hard-to-transfect leukemic cells, and their function was dually validated with the addition of MYBL2 and IDH2 genes into HEK293 cells. We then successfully modified the MYBL2 gene and introduced the R172 mutation into the IDH2 gene within NB4 and HL60 cells that constitutively expressed the Cas9 nuclease. The efficiency of mutation introduction with our methodology was similar to that of ribonucleoprotein strategies, and no off-target events were detected. Overall, our strategy represents a valid and intuitive alternative for introducing desired mutations into hard-to-transfect leukemic cells without viral transduction.

NUTRARET: Effect of 2-Year Nutraceutical Supplementation on Redox Status and Visual Function of Patients With Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress plays a major role in the pathogenesis of retinitis pigmentosa (RP). The main goal of this study was to evaluate the effect of 2-year nutritional intervention with antioxidant nutraceuticals on the visual function of RP patients. Secondly, we assessed how nutritional intervention affected ocular and systemic redox status. We carried out a randomized, double-blind, placebo-controlled study. Thirty-one patients with RP participated in the study. RP patients randomly received either a mixture of nutraceuticals (NUT) containing folic acid, vitamin B6, vitamin A, zinc, copper, selenium, lutein, and zeaxanthin or placebo daily for 2 years. At baseline and after 2-year of the nutritional supplementation, visual function, dietetic-nutritional evaluations, serum concentration of nutraceuticals, plasma and aqueous humor concentration of several markers of redox status and inflammation were assessed. Retinal function and structure were assessed by multifocal electroretinogram (mfERG), spectral domain-optical coherence tomography (SD-OCT) and automated visual field (VF) tests. Nutritional status was estimated with validated questionnaires. Total antioxidant capacity, extracellular superoxide dismutase (SOD3), catalase (CAT), and glutathione peroxidase (GPx) activities, protein carbonyl adducts (CAR) content, thiobarbituric acid reactive substances (TBARS) formation (as indicator of lipid peroxidation), metabolites of the nitric oxide (NOX) and cytokine (interleukin 6 and tumor necrosis factor alpha) concentrations were assessed by biochemical and immunological techniques in aqueous humor or/and blood. Bayesian approach was performed to determine the probability of an effect. Region of practical equivalence (ROPE) was used. At baseline, Bayesian analysis revealed a high probability of an altered ocular redox status and to a lesser extent systemic redox status in RP patients compared to controls. Twenty-five patients (10 in the treated arm and 15 in the placebo arm) completed the nutritional intervention. After 2 years of supplementation, patients who received NUT presented better retinal responses (mfERG responses) compared to patients who received placebo. Besides, patients who received NUT showed better ocular antioxidant response (SOD3 activity) and lower oxidative damage (CAR) than those who received placebo. This study suggested that long-term NUT supplementation could slow down visual impairment and ameliorate ocular oxidative stress.

Novel mutations in the USH1C gene in Usher syndrome patients.

PURPOSE: Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by severe-profound sensorineural hearing loss, retinitis pigmentosa, and vestibular areflexia. To date, five USH1 genes have been identified. One of these genes is Usher syndrome 1C (USH1C), which encodes a protein, harmonin, containing PDZ domains. The aim of the present work was the mutation screening of the USH1C gene in a cohort of 33 Usher syndrome patients, to identify the genetic cause of the disease and to determine the relative involvement of this gene in USH1 pathogenesis in the Spanish population. METHODS: Thirty-three patients were screened for mutations in the USH1C gene by direct sequencing. Some had already been screened for mutations in the other known USH1 genes (myosin VIIA [MYO7A], cadherin-related 23 [CDH23], protocadherin-related 15 [PCDH15], and Usher syndrome 1G [USH1G]), but no mutation was found. RESULTS: Two novel mutations were found in the USH1C gene: a non-sense mutation (p.C224X) and a frame-shift mutation (p.D124TfsX7). These mutations were found in a homozygous state in two unrelated USH1 patients. CONCLUSIONS: In the present study, we detected two novel pathogenic mutations in the USH1C gene. Our results suggest that mutations in USH1C are responsible for 1.5% of USH1 disease in patients of Spanish origin (considering the total cohort of 65 Spanish USH1 patients since 2005), indicating that USH1C is a rare form of USH in this population.

Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with idiopathic acute anterior uveitis.

PURPOSE: The purpose of this study was to evaluate the levels of neutrophil gelatinase-associated lipocalin (NGAL) in the aqueous humor in eyes with idiopathic acute anterior uveitis (AAU). METHODS: A comparative control study. Aqueous humor was collected from 20 eyes of 20 patients with idiopathic AAU. The control group included 20 aqueous samples from 20 patients about to undergo cataract surgery and without any other ocular or systemic diseases. The level of NGAL was determined with a commercially available ELISA kit. RESULTS: The concentration of NGAL in aqueous humor was markedly higher in patients with idiopathic AAU than in control subjects (Mann-Whitney U test, p<0.001). The level of NGAL was 139,197.38+/-183,426.36 (mean+/-SD) pg/ml in eyes with AAU and 3,169.96+/-1,595.78 pg/ml in the eyes of the control group. CONCLUSIONS: The aqueous humor NGAL level is increased in eyes with idiopathic AAU. These results imply that NGAL is associated with the regulation of inflammation in patients with AAU and could be used as a biomarker of ocular inflammation and immunomodulatory treatment response.

Ruptured dissecting cerebral aneurysms in young people: report of three cases.

Intracranial arterial aneurysms in the pediatric population are rare. Among these, dissecting aneurysms are the most frequent, followed by saccular, infectious, and posttraumatic. It is widely known that aneurysmal rupture is uncommon in the first two decades of life. Spontaneous dissecting aneurysms (SDAs) of the middle cerebral artery (MCA) affecting young individuals most frequently present as occlusive syndrome with ischemia, although bleeding and subarachnoid hemorrhage can also occur. Between March 2006 and January 2008, three young patients (20 months, 8 and 20 years old) were surgically treated for MCA SDA in the Neurosurgical Department of "12 de Octubre" Hospital of Madrid. These patients showed hemorrhage as primary radiological finding, and all of them underwent surgical operation. Aneurysms were always treated by trapping, with aneurysmectomy in one case, but no distal extra-intracranial (EC-IC) bypass was performed. In two cases, the histological examination of the aneurysm's wall evidenced signs of subintimal dissection with widespread disruption of the internal elastic lamina and media with neointima formation and intramural hemorrhage. Although bleeding is an uncommon presenting sign of SDAs, they should be suspected in young people showing hemorrhage at CT scan. Early surgical treatment and, if possible, preoperative neuroimaging evaluation of intracranial vessels should be performed to reduce the mortality in these patients despite a higher postoperative morbidity. From a technical point of view, surgical trapping of the aneurysm seems to be a reasonable treatment strategy especially in an emergency basis. However, whenever possible, an EC-IC bypass could help diminish the ischemic morbidity associated with these aneurysms.

Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?

Huntington disease (HD) is a neurodegenerative condition and one of the so-called rare or minority diseases, due to its low prevalence (affecting 1-10 of every 100,000 people in western countries). The causative gene, HTT, encodes huntingtin, a protein with a yet unknown function. Mutant huntingtin causes a range of phenotypes, including oxidative stress and the activation of microglia and astrocytes, which leads to chronic inflammation of the brain. Although substantial efforts have been made to find a cure for HD, there is currently no medical intervention able to stop or even delay progression of the disease. Among the many targets of therapeutic intervention, oxidative stress and inflammation have been extensively studied and some clinical trials have been promoted to target them. In the present work, we review the basic research on oxidative stress in HD and the strategies used to fight it. Many of the strategies to reduce the phenotypes associated with oxidative stress have produced positive results, yet no substantial functional recovery has been observed in animal models or patients with the disease. We discuss possible explanations for this and suggest potential ways to overcome it.

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration.

: Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying some groups of rare diseases: Friedreich's ataxia, diseases with neurodegeneration with brain iron accumulation, Charcot-Marie-Tooth as an example of rare neuromuscular disorders, inherited retinal dystrophies, progressive myoclonus epilepsies, and pediatric drug-resistant epilepsies. Despite the discrimination between cause and effect may not be easy on many occasions, all these conditions are Mendelian rare diseases that share oxidative stress as a common factor, and this may represent a potential target for therapies.

Degrees of tolerance in post-traumatic orbital volume correction: the role of prefabricated mesh.

PURPOSE: To identify factors influencing the volumetric correction of orbital fractures, and evaluate the use of prefabricated titanium mesh in their repair. MATERIALS AND METHODS: We included patients with unilateral orbital fractures and floor or medial-wall defects, subsequently reconstructed with titanium mesh, and subject to adequate follow-up with multislice, digitalized computed tomography (CT) images. Medical records were reviewed, and demographics, operative details, and postoperative course were recorded as prognostic variables. Moreover, orbital volume, apex-to-globe distance, and orbital rim area were measured using postoperative CT. Univariate analysis and a multiple-regression model were used to identify associated factors. RESULTS: A total of 32 patients fulfilled the inclusion criteria. Postoperative clinical evaluation and CT images were obtained in a mean +/- SD of 12.3 +/- 7.2 months after surgery. Clinically, 20 patients were considered normal (63%), and 12 manifested some ocular dystopia (37%). On postoperative CT, the mesh was in good position in 44% of cases, and in an insufficient position in 56% of cases. There was a significant difference between fractured and normal orbits in relation to orbital volume and apex-globe distance. Clinical evaluation significantly correlated with CT mesh placement, but there was no correlation between clinical evaluation and any of the variables measured on CT. The most important factors influencing postoperative orbital volume correction were type of fracture, affected walls, and use of prefabricated mesh. CONCLUSION: Volumetric and lineal symmetry between fractured and normal orbits are very difficult to achieve. In this study, postoperative CT measurements did not correlate with subjective clinical assessment. The clinical-radiological disagreement may be explained by measurement accuracy problems, clinical bias, or normal differences between orbits. The most important identified modifiable factor was the use of prefabricated mesh.

Metformin treatment reduces motor and neuropsychiatric phenotypes in the zQ175 mouse model of Huntington disease.

Huntington disease is a neurodegenerative condition for which there is no cure to date. Activation of AMP-activated protein kinase has previously been shown to be beneficial in in vitro and in vivo models of Huntington's disease. Moreover, a recent cross-sectional study demonstrated that treatment with metformin, a well-known activator of this enzyme, is associated with better cognitive scores in patients with this disease. We performed a preclinical study using metformin to treat phenotypes of the zQ175 mouse model of Huntington disease. We evaluated behavior (motor and neuropsychiatric function) and molecular phenotypes (aggregation of mutant huntingtin, levels of brain-derived neurotrophic factor, neuronal inflammation, etc.). We also used two models of polyglutamine toxicity in Caenorhabditis elegans to further explore potential mechanisms of metformin action. Our results provide strong evidence that metformin alleviates motor and neuropsychiatric phenotypes in zQ175 mice. Moreover, metformin intake reduces the number of nuclear aggregates of mutant huntingtin in the striatum. The expression of brain-derived neurotrophic factor, which is reduced in mutant animals, is partially restored in metformin-treated mice, and glial activation in mutant mice is reduced in metformin-treated animals. In addition, using worm models of polyglutamine toxicity, we demonstrate that metformin reduces polyglutamine aggregates and restores neuronal function through mechanisms involving AMP-activated protein kinase and lysosomal function. Our data indicate that metformin alleviates the progression of the disease and further supports AMP-activated protein kinase as a druggable target against Huntington's disease.

Spatial and temporal trends of marine litter in the Spanish Mediterranean seafloor.

Composition, spatial distribution and temporal evolution of marine litter on the Spanish Mediterranean seafloor were assessed. The data derive from Spanish MEDITS surveys over 11 years and were analysed by GIS. A total amount of 2197.8 kg of litter was collected. Marine litter (by weight) was composed of plastics (29.3%), clinker (28.4%), wood (10.2%), metal (9.7%) and glass (6.2%). Its density varied among Areas (Alboran Sea > Valenciana >Alboran Island > Tramontana). For the last 11 years, the marine litter has remained stable or decreases in some case. The information provided by this study is a useful baseline to study such debris on the Spanish seafloor. The MEDITS survey has proven to be an appropriate monitoring tool, also of use to assess future control measures.

Establishment of a human iPSC line, IISHDOi004-A, from a patient with Usher syndrome associated with the mutation c.2276G>T; p.Cys759Phe in the USH2A gene.

A human iPSC line, IISHDOi004-A, from fibroblasts obtained from a patient with Usher syndrome, harboring a homozygous mutation in the USH2A gene (c.2276G>T; p.Cys759Phe) has been generated. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.

Spectrum of the ABCA4 gene mutations implicated in severe retinopathies in Spanish patients.

PURPOSE: The purpose of this study is to describe the spectrum of mutations in the ABCA4 gene found in Spanish patients affected with several retinal dystrophies. METHODS: Sixty Spanish families with different retinal dystrophies were studied. Samples were analyzed for variants in all 50 exons of the ABCA4 gene by screening with the ABCR400 microarray, and results were confirmed by direct sequencing. Haplotype analyses were also performed. For those families with only one mutation detected by the microarray, denaturing (d)HPLC was performed to complete the mutational screening of the ABCA4 gene. RESULTS: The sequence analysis of the ABCA4 gene led to the identification of 33 (27.5%) potential disease-associated alleles among the 60 patients. These comprised 16 distinct sequence variants in 25 of the 60 subjects investigated. For autosomal recessive cone-rod dystrophy (arCRD), we found that 50% of the CRD families with the mutation had two recurrent changes (2888delG and R943Q). For retinitis pigmentosa (RP) and autosomal dominant macular dystrophy (adMD), one putative disease-associated allele was identified in 9 of the 27 and 3 of the 7 families, respectively. CONCLUSIONS: In the population studied, ABCA4 plays an important role in the pathogenesis of arCRD. However, mutations in this gene are less frequently identified in other retinal dystrophies, like RP or adMD, and therefore it is still not clear whether ABCA4 is involved as a modifying factor or the relationship is a fortuitous association.

Composition, spatial distribution and sources of macro-marine litter on the Gulf of Alicante seafloor (Spanish Mediterranean).

The composition, spatial distribution and source of marine litter in the Spanish Southeast Mediterranean were assessed. The data proceed from a marine litter retention programme implemented by commercial trawlers and were analysed by GIS. By weight, 75.9% was plastic, metal and glass. Glass and plastics were mainly found close to the coast. A high concentration of metal was observed in some isolated zones of both open and coastal waters. Fishing activity was the source of 29.16% of the macro-marine litter, almost 68.1% of the plastics, and 25.1% of the metal. The source of the other 60.84% could not be directly identified, revealing the high degree of uncertainty regarding its specific origin. Indirectly however, a qualitative analysis of marine traffic shows that the likely sources were merchant ships mainly in open waters and recreational and fishing vessels in coastal waters.