Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons.

Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a's function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.

Physicochemical Characterisation of Seeds, Oil and Defatted Cake of Three Hempseed Varieties Cultivated in Spain.

The increasing use of hempseed in food products highlights the need for a comprehensive database for scientific research and industrial applications. In food development, information about the techno-functional properties of raw materials plays a crucial role in determining the suitability of each product for specific applications. Thus, this study aims to characterise three hempseed varieties (Ferimon, Henola and Uso-31), comparing their physicochemical and nutritional compositions. Moreover, the study investigates the impact of hempseed varieties on the techno-functional, physical and thermal properties of the partially defatted hempseed flours (PDHFs) obtained from single screw pressing (SSP) oil extraction. The fatty acid and tocopherol profiles of the dehulled seeds and oil were also analysed. Significant variations in yield and physical properties were observed among hempseed varieties, influenced by genetics, adaptation to agro-climatic conditions and cultivation systems. Despite its lower yield (kg/ha), Uso-31 exhibited superior 1000-seed weight, dehulling yield and larger mean seed size (1.79 ± 0.02 mm). Hempseed oil was rich in unsaturated fatty acids, particularly linoleic (51.2-53.4 g/100 g oil) and α-linolenic (14.88-18.97 g/100 oil) acids, showing variations in γ- and α-tocopherols depending on the variety. The variety also influenced the least gelation concentration (LGC) and techno-functional properties such as water absorption capacity (WAC), emulsifying activity (EA) and emulsion stability (ES). SDS-PAGE and DSC measurements indicated the presence of 11S and 7S globulin proteins with denaturation temperatures above 87.8 °C. These findings confirm that the studied hempseed flours are valuable techno-functional and nutritional ingredients suitable for sustainable food formulations.

Three-Dimensional Volume Rendering in Computed Tomography for Evaluation of the Temporomandibular Joint in Dogs.

Based on computed tomography (CT) images, volume rendering was used to obtain a three-dimensional representation of data (3DVR). The aims of this study included: describing the bone anatomy of the temporomandibular joint (TMJ) of dogs; comparing the TMJs of each dog by skull type and age; comparing 3DVR images with three-standard-plane CTs; assessing soft tissues adjacent to the TMJ and assessing pathological cases. Multidetector computed tomography scans of bilateral TMJs of 410 dogs were observed. From a ventral view, slight displacements in the positions of the skulls were seen, whereas from a caudal view, differences in amplitude of the articular space were observed. Dolichocephalic and mesaticephalic dogs showed more similar TMJ features than brachycephalic dogs. The shape of the TMJ bones were irregular in dogs under 1 year old. The 3DVR images related to the three-standard-plane CT improved the overall comprehension of the changes in the articular space amplitude and condylar process morphology. The fovea pterygoidea, mandibular fossa and retroarticular process were perfectly shown. A better spatial situation of adjacent soft tissues was obtained. The 3DVR represents an ancillary method to the standard-plane CT that could help in the understanding of the anatomy and diagnoses of different pathologies of the TMJ in dogs.

Uso de Nobecutan® para la cura de vías centrales / Use of Nobecutan® for the cure of central venous catheters

El uso de catéteres venosos centrales para facilitar el manejo de los pacientes después de una cirugía mayor es muy f recuente. Los profesionales de enfermería son los responsables de su cuidado, manipulación y mantenimiento, jugando, por lo tanto, un papel muy importante para disminuir la incidencia de infecciones. Metodología: estudio descriptivo y longitudinal sobre un total de 14 pacientes portadores de catéteres, donde 7 de ellos fueron curados con cura tradicional (gasas estériles impregnadas de clorhexidina + apósito transparente) y otros 7 con cura experimental (gasas estériles impregnadas de clorhexidina + nobecutan® spray + apósito transparente). Resultados: los grupos fueron bastante homogéneos en cuanto a edad y sexo, encontrando sin embargo bastantes diferencias en lo relativo a la frecuencia de las curas, el dolor referido y la valoración de la piel pericatéter, obteniendo mejores resultados en el grupo en el cual se emplea nobecutan® spray. Conclusión: el uso de nobecutan® spray para la cura de catéteres venosos centrales es beneficioso a tres niveles, ya que disminuye el dolor y la frecuencia de las curas, y con ello la manipulación y por lo tanto el riesgo de infección. (AU)

The use of central venous catheters for the management of patients after major surgery is very common. Nursing professionals are responsible for the care, handling and maintenance of these catheters, playing an important role in preventing the incidence of infections. Methodology: Descriptive and longitudinal study of a total of fourteen cases of patients with central venous catheters, where seven of them were cured with traditional cure (sterile gauze impregnated with chlorhexidine and transparent dressing) and another seven with experimental cure (sterile gauze impregned with chlorhexidine and nobecutan® spray and transparent dressing). Results: The groups were quite homogeneous in terms of age and sex of patients, finding significant differences in the frequency of cures, patient pain and rating of the pericatheter skin; being much more beneficial in the group where nobecutan® spray was used for the cure. Conclusion: The use of nobecutan® spray for the treatment of central catheters is beneficial at three levels since it reduces pain. The risk of infection is lower as the frequency of treatment, manipulation decreases. (AU)

Rhinomanometry with and without decongestant used to select children for adenoidectomy: a cohort study.

OBJECTIVE: Adenoid hypertrophy may coexist, and often does, with rhinitis. Therefore, in some cases, adenoidectomy alone, despite the fact that it reduces nasal resistance, may be insufficient to restore nasal breathing. Juliusson et al. suggested using rhinomanometry with and without nasal decongestant as a method for selecting patients for adenoidectomy. In this study, we aim to assess whether the decongestant test, when using normative data, is useful to select children for adenoidectomy. METHODS: Children between 4 and 15 years old undergoing adenoidectomy were selected from two tertiary referral university hospitals. Participants underwent anterior active rhinomanometry with and without nasal decongestant before and after surgery. Parents fill in the sinus and nasal quality-of-life survey (SN5). RESULTS: 47 participants were included, and mean age 6.5 ± 2.15. 2 cohorts were defined according to the result of the nasal decongestant test (> 40% improvement in nasal resistance or not). There is a statistically significant difference between groups, with a higher improvement in nasal resistance and airflow after adenoidectomy in the group with less than 40% improvement in nasal resistance. CONCLUSIONS: In conclusion, this study supports the use of the decongestant test with rhinomanometry to select children for adenoidectomy; especially as it has proven to be a simple technique, harmless, fast, and easily performed on collaborative children.

CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages.

The paralogous lysine acetyltransferases 3 (KAT3), CBP and P300, play critical roles during neurodevelopment, but their specific roles in neural precursors maintenance and differentiation remain obscure. In fact, it is still unclear whether these proteins are individually or jointly essential in processes such as proliferation of neural precursors, differentiation to specific neural cell types, or both. Here, we use subventricular zone-derived neurospheres as a potential ex vivo developmental model to analyze the proliferation and differentiation of neural stem cells (NSCs) lacking CBP, p300, or both proteins. The results showed that CBP and p300 are not individually essential for maintenance and proliferation of NSCs, although their combined ablation seriously compromised cell division. In turn, the absence of either of the two proteins compromised the differentiation of NSC into the neuronal and astrocytic lineages. Single-nucleus RNA sequencing analysis of neural cell cultures derived from CBP or p300 mutant neurospheres revealed divergent trajectories of neural differentiation upon CBP or p300 ablation, confirming unique functions and nonredundant roles in neural development. These findings contribute to a better understanding of the shared and individual roles of KAT3 proteins in neural differentiation and the etiology of neurodevelopmental disorders caused by their deficiency.

CBP Is Required for Establishing Adaptive Gene Programs in the Adult Mouse Brain.

Environmental factors and life experiences impinge on brain circuits triggering adaptive changes. Epigenetic regulators contribute to this neuroadaptation by enhancing or suppressing specific gene programs. The paralogous transcriptional coactivators and lysine acetyltransferases CREB binding protein (CBP) and p300 are involved in brain plasticity and stimulus-dependent transcription, but their specific roles in neuroadaptation are not fully understood. Here we investigated the impact of eliminating either CBP or p300 in excitatory neurons of the adult forebrain of mice from both sexes using inducible and cell type-restricted knock-out strains. The elimination of CBP, but not p300, reduced the expression and chromatin acetylation of plasticity genes, dampened activity-driven transcription, and caused memory deficits. The defects became more prominent in elderly mice and in paradigms that involved enduring changes in transcription, such as kindling and environmental enrichment, in which CBP loss interfered with the establishment of activity-induced transcriptional and epigenetic changes in response to stimulus or experience. These findings further strengthen the link between CBP deficiency in excitatory neurons and etiopathology in the nervous system.SIGNIFICANCE STATEMENT How environmental conditions and life experiences impinge on mature brain circuits to elicit adaptive responses that favor the survival of the organism remains an outstanding question in neurosciences. Epigenetic regulators are thought to contribute to neuroadaptation by initiating or enhancing adaptive gene programs. In this article, we examined the role of CREB binding protein (CBP) and p300, two paralogous transcriptional coactivators and histone acetyltransferases involved in cognitive processes and intellectual disability, in neuroadaptation in adult hippocampal circuits. Our experiments demonstrate that CBP, but not its paralog p300, plays a highly specific role in the epigenetic regulation of neuronal plasticity gene programs in response to stimulus and provide unprecedented insight into the molecular mechanisms underlying neuroadaptation.

Evaluation of the ACTH stimulation test using a low dose of a depot formulation in healthy dogs and in dogs with untreated Cushing's syndrome.

The sensitivity of the adrenocorticotropic hormone (ACTH) stimulation test to detect Cushing's Syndrome (CS) using a depot formulation needs to be evaluated. The aims of this study were to propose a reference interval (RI) for cortisol values 1-hour after administration of a low-dose of depot ACTH in healthy dogs, and to evaluate the sensitivity of this test to detect CS, differentiating among types of CS based on ultrasound findings. Forty-one healthy dogs (20 males, 21 females) were prospectively included. Additionally, 90 dogs with CS (31 males, 59 females) were retrospectively included. Dogs with CS were ultrasonographically classified as follows: 44 dogs with symmetrical adrenomegaly consistent with pituitary-dependent hypercortisolism (PDH), 8 dogs with unilateral adrenomegaly and atrophy of the contralateral adrenal gland or unilateral or bilateral adrenomegaly with malignancy features consistent with adrenal-dependent hypercortisolism (ADH), 34 dogs with equivocal adrenal asymmetry (EAA) and 4 dogs with normal adrenal thickness. In healthy dogs, lower and upper limit of the 95% RI for 1-hour post-ACTH cortisol concentration and their 90% confidence intervals, were 4.4 (2.7-5.8) µg/dl and 18.4 (16.5-20.0) µg/dl, respectively. Post-ACTH cortisol concentration was above the RI in 90.0% (ci95%, 76.1-100) of dogs with CS. An elevated post-ACTH cortisol concentration was detected in 95.5% (ci95%, 76.1-100) of dogs with PDH, 62.5% (ci95%, 46.1-78.9) of dogs with ADH and 88.2% (ci95%, 69.1-100) of dogs with EAA. The sensitivity of the ACTH stimulation test using a low-dose of depot ACTH in high in dogs with CS.

New Applications of Photodynamic Therapy in the Management of Candidiasis.

The most important aetiological agent of opportunistic mycoses worldwide is Candida spp. These yeasts can cause severe infections in the host, which may be fatal. Isolates of Candida albicans occur with greater frequency and variable resistance patterns. Photodynamic therapy (PDT) has been recognised as an alternative treatment to kill pathogenic microorganisms. PDT utilises a photosensitizer, which is activated at a specific wavelength and oxygen concentration. Their reaction yields reactive oxygen species that kill the infectious microorganism. A systematic review of new applications of PDT in the management of candidiasis was performed. Of the 222 studies selected for in-depth screening, 84 were included in this study. All the studies reported the antifungal effectiveness, toxicity and dosimetry of treatment with antimicrobial PDT (aPDT) with different photosensitizers against Candida spp. The manuscripts that are discussed reveal the breadth of the new applications of aPDT against Candida spp., which are resistant to common antifungals. aPDT has superior performance compared to conventional antifungal therapies. With further studies, aPDT should prove valuable in daily clinical practice.

Attitudes of Spanish hospital staff towards COVID-19 vaccination and vaccination rates.

BACKGROUND: COVID-19 vaccine hesitancy seems to be universal across countries and subgroups, and so are its determinants. We studied the willingness and factors associated with the decision to be vaccinated against COVID-19 in healthcare workers (HCW) in a Spanish tertiary hospital. Furthermore, we compared the percentage of willingness to vaccinate against COVID with actual vaccination rates among HCW in our hospital. METHODS: From December 21, 2020 to January 4, 2021, before initiation of the COVID-19 HCW vaccination campaign at Germans Trias i Pujol University Hospital (HUGTiP), an anonymous self-administered questionnaire was administered to HCW. Univariate and multivariate logistic regression of the association of variables with the outcome "intention to receive the COVID-19 vaccine as soon as possible" was conducted. Vaccination rates were extracted from the hospital information systems. RESULTS: Forty-four percent of HCW included in the study declared a willingness to be vaccinated against COVID-19 as soon as possible. This was associated with male sex [1.66 (95%CI 1.13-2.43); p = 0.009], older age [1.02 (95%CI 1.00-1.03); p = 0.014], belonging to the occupational groups "physician" or "other" [5.76 (95%CI 3.44-9.63) and 2.15 (95%CI 1.25-3.70); p<0.001], respectively, and reporting influenza vaccination during the last three seasons or at least one of the last three seasons [3.84 (95%CI 2.56-5.75) and 2.49 (95%CI 1.71-3.63); p<0.001]. One in ten hospital workers reported they were unwilling to receive COVID-19 vaccination. Actual COVID-19 vaccination uptake among HCW was higher (80.4%) than the percentage of willingness to vaccinate estimated from the questionnaire. Physicians not only had the highest vaccination rate, but also the highest correlation between the reported intention to vaccinate and the final decision to receive COVID-19 vaccination. CONCLUSIONS: COVID-19 vaccination uptake was higher than previously estimated according to the stated intentions of HCW. Doubts and fears must be addressed, particularly in persons less inclined to be vaccinated: females, younger people and those not vaccinated against influenza in recent seasons. The study of barriers and strategies aimed at promoting COVID-19 vaccination must be adapted in relation to occupational groups' attitudes, understanding their idiosyncrasies with respect to this and other vaccines.

What is the relationship between the size of the adenoids and nasal obstruction? A systematic review.

OBJECTIVE: adenoidectomy is one of the most common surgical procedure in pediatric otolaryngology practice. Clinical guidelines (such as the Spanish or American) suggest adenoidectomy when the enlargement of the adenoids is associated with nasal obstruction. Nasal endoscopy and cephalograms are adequate methods to estimate the size of the adenoids. However, they do not measure nasal patency. This systematic review is designed with the objective of exploring the relationship between adenoid size and nasal ventilation through rhinomanometry. REVIEW METHODS: 3 authors members of the YO-IFOS rhinology study group independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing both nasal resistance and/or nasal airflow in rhinomanometry and adenoid size by any method (endoscopy, cephalogram, direct examination). RESULTS: A total of 10 studies with a total population of 969 participants met the inclusion criteria. 5 authors explored the size of the adenoids through endoscopy. 4 authors explored the adenoids through lateral cephalograms. Finally, a further 2 authors explored adenoid size studying the resected tissue. Five studies explored the correlation between adenoid size and nasal resistance in rhinomanometry, which ranged from 0.20 to 0.84. Finally, 5 studies used nasal decongestant. It was found higher sensitivity and specificity, a higher area under the curve for the receiver operating characteristic curve, and higher correlation with adenoid size for rhinomanometry under nasal decongestion. CONCLUSION: Up to now, there is no ideal diagnostic method for adenoid hypertrophy. Therefore, it seems prudent to use a combination of all currently available tools, as they provide complementary, rather than supplementary information. Available evidence suggests that rhinomanometry combined with nasal decongestant could help to elucidate the existence of nasal obstruction in intermediate cases of adenoid hypertrophy, as well as throw light on other possible causes for nasal obstruction, mainly turbinate hypertrophy.

Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes.

Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gainslength+%losseslength), (2) copy number load (CNL) (%gainslength-%losseslength) and (3) net genomic load (NGL) (%gainsamount-%lossesamount). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with Cox regression. We identified 38% of HR-NB patients with poor 5-year OS. A negative CNL genomic background was related to poor prognosis in patients ≥18 months showing tumors with homogeneous MYCN amplification (9.5% survival probability, P < 0.05) and patients with non-MYCN amplified NB (18.8% survival probability related to >2.4% CNL, P < 0.01). A positive CNL genomic background was associated with worse outcome in patients with heterogeneous MYCN amplification (22.5% survival probability, P < 0.05). We conclude that characterizing a tumor genomic background according to predominance of genome gained or lost contributes toward improved outcome prediction and brings greater insight into the tumor biology of HR-NB patients.

Subcritical Water Extraction of Phenolic Compounds from Onion Skin Wastes (Allium cepa cv. Horcal): Effect of Temperature and Solvent Properties.

The valorization of onion skin wastes (OSW) through the extraction, identification, and quantification of phenolic compounds was studied in this work, using subcritical water in a semicontinuous extractor (2.5 mL/min; 105-180 °C; 5 MPa). The extraction of flavonoids resulted to be fast (<30 min) and temperature sensitive (maximum at 145 °C; total flavonoids, 27.4 ± 0.9 mg/g dry OSW (DOSW)). The experimental results were fitted to the Weibull model. The influence of the solvent properties on the flavonoids quantification was found to be critical. A precipitate was formed once the extracts cooled down. If removed, a significant fraction of the high temperature extracted flavonoids (as much as 71%, at 180 °C) was lost. Such a condition affected especially those compounds that show extremely low solubility in water at room temperature, whereas quercetin glycosylated derivatives were less affected by the polarity change of the medium induced by the temperature change. It was demonstrated that it is necessary to re-dissolve the subcritical water extracts by the addition of ethanol, which led to a medium with a polarity equivalent to that obtained with water at high temperature. At 145 °C, quercetin (15.4 ± 0.4 mg/g DOSW) and quercetin-4'-glucoside (8.4 ± 0.1 mg/g DOSW) accounted for the 90% of the total flavonoids identified. By recovering high added value bioactive compounds from OSW the principles of circular economy were fulfilled, providing a new use for this agricultural waste.

Scoping Review of Kaizen and Green Practices: State of the Art and Future Directions.

Given the importance that environmental management is acquiring, the main aim of this work is to know what the state of the field kaizen and green practices is at present. A systematic narrative review is conducted in accordance with the PRISMA Statement. Two databases (Web of Science and Scopus) were searched. Finally, after applying the defined inclusion and exclusion criteria, 19 documents were analyzed. Based on the results, it might be concluded that, despite the growing interest in the relationship between kaizen and green practices, this is a topic in the early stages of development, with a clear predominance of case studies. It is, therefore, necessary to develop more research on this kaizen and green issue as improving environmental management is undeniably becoming a must in today's competitive environment. For instance, more research is needed on the application of kaizen tools as results obtained so far seem not to be conclusive. Additionally, more academic and rigorous studies should be developed on this topic as many of the analyzed papers seem to be clearly created for dissemination among practitioners, some of them lacking the traditional academic structure and scientific method during their development.

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line.

BACKGROUND: Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. METHODS: We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK-mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. RESULTS: We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. CONCLUSIONS: Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

Cross-cultural adaptation of the sinus and nasal quality of life survey (SN-5) to Spanish.

OBJECTIVE: There is a high prevalence for rhinitis with an increasing trend. However, there is a lack of specific quality of life pediatric questionnaires for sinonasal symptoms. The Sinus and Nasal Quality of Life Survey (SN-5) is the only validated instrument specifically designed with this objective. In this work we have translated and validated the Spanish version of the SN5 questionnaire. METHODS: The SN5 was translated according to the World Health Organization recommendation for the translation and adaptation of instruments. The final version of the Sp-SN5 was administered twice (day 0 and day 7) to 137 participants with and without sinonasal symptoms. Reliability was measured with Cronbach α, temporal stability was measured with intraclass correlation coefficient. External validity was assessed with a ROC curve comparing a cohort of cases (children going to turbinate radiofrequency ablation) and controls (asymptomatic children). RESULTS: A Spearman correlation between the total result of the Sp-SN-5 questionnaire and the QOL score showed a strong negative correlation in the general sample and all the age subgroups. Internal consistency measured with Cronbach α was 0.87 for 5 items and was still over 0.83 after removing each item of the test. The intraclass correlation coefficient (ICC) for test-retest measurements was 0.94. The receiver operating characteristic (ROC) curve for all the included participants showed a very high area under the curve (0.998). CONCLUSIONS: The Sp-SN-5 questionnaire was successfully translated and cross-culturally adapted into Spanish, and the translated version exhibited adequate properties. The survey was effective in assessing the quality of life of pediatric patients with sinonasal complaints and can be used for this purpose both in a clinical setting and in future research.

Specific seismic retrofitting of a compact reinforced concrete building with X-bracings and steel jackets. Application to a primary school in Huelva.

Previous research has indicated that many European buildings are vulnerable to moderate-magnitude earthquakes. For example, during the L´Aquila (Italia, Mw 6.3, 2009) and Lorca (Spain, Mw 5.9, 2011) earthquakes, many old buildings were severely damaged and some of them collapsed. In specific, significant damage has been found in several school buildings after past earthquakes in Europe. This is due to the fact that many of them were constructed prior to the current seismic codes, thus considering only gravitational loads and with no seismic design whatsoever. Primary schools are even more vulnerable than other typologies because of their low adult/child ratio. The seismic activity of the Iberian Peninsula is low-moderate. However, the Algarve and Huelva regions, which are situated in the south-west, are influenced by large faults which have caused major earthquakes of long-return periods. The European project PERSISTAH (Projetos de Escolas Resilientes aos SISmos no Território do Algarve e de Huelva, in Portuguese) aims to cooperatively evaluate the seismic vulnerability of primary schools in the Algarve (Portugal) and Huelva (Spain) regions. The present work is framed under this project. The objective of this paper is to determine the most effective retrofitting scheme for a typical primary school building in this area, considering structural, architectural and constructive parameters. The scheme could be applied to several buildings of the same typology, decreasing costs and time. An existing reinforced concrete frame building has been selected for the study. This is one of the most commonly used typologies for primary schools in this area. A nonlinear static analysis has been carried out in order to study its seismic behaviour. The performance point of the building has been obtained through the capacity-demand spectrum method. The preliminary results have confirmed the poor seismic behaviour of this building. Specifically, soft-story behaviour has been identified in the ground floor and short columns have been observed in the upper floors. Therefore, specific seismic retrofitting solutions have been proposed and evaluated in order to identify the one that is the most efficient. The combination of reinforcements has been done considering the structural and architectural impact and constructive parameters. The calculations have shown that steel X-bracings are the best solution for preventing the formation of a soft-storey in the ground floor. Unfortunately, this scheme increases the deformation in the upper floor columns. The best solution for the upper floors' short columns has been the use of steel jackets. The results have also shown that this combination produces an important reduction of the expected general damage level. The resulting retrofitting scheme can be extrapolated to other buildings with a similar typology.

KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain.

The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions.