How lipid nanocarriers improve transdermal delivery of olanzapine

The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach

Zebrafish as a disease model for studying human Rett Syndrome

Background: Rett syndrome (RTT) is a severe neurological disorder that affects almost exclusively females. This disease is characterized by normal growth and intellectual development until around the first year, then progression in development starts to slow down, with loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability. Mutations in the X-linked genes methyl-CpG-binding protein 2 (MECP2) and cyclin-dependent kinase-like 5 (CDKL5) were described in RTT and recently several bone diseases related with decreased bone mass were also described in those patients, starting early in life. Because zebrafish was largely validated as a model for human diseases, the main objective of this work was to investigate if zebrafish can be a good model to study RTT

Characterisation of Portuguese RC precast industrial building stock

The construction of a vulnerability model requires reliable information on the features of the buildings in the study. The purpose of this work is the characterisation of the precast industrial buildings in Portuguese industrial park, based on the survey of 73 design projects of existing buildings. The collected data are based on a previous study on the features that influence the seismic response of this type of buildings. The parameters collected are associated with the global geometry and specific elements characteristics (e.g., column dimensions, reinforcement ratios, and connections details), to the mechanical properties of the materials and other parameters that can give some important information in the characterisation of the buildings (e.g., construction year and localization). In the end, a comparison with other available databases, namely, from Italy and Turkey, is done in order to conclude about the similarity. This information is important to define representative experimental specimens and numerical simulation to conduce seismic risk analysis.publishe

Two DOT1 enzymes cooperatively mediate efficient ubiquitin-independent histone H3 lysine 76 tri-methylation in kinetoplastids

In higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (G

Campos nativos e matas adjacentes da região de Humaitá (AM): atributos diferenciais dos solos.

Objetivou-se no presente trabalho estabelecer algumas razões da estratificação ambiental entre mata e campo nativo na região de Humaitá (AM). Para tanto, foram observados morfologicamente e amostrados 10 perfis de solos, sendo 5 perfis sob mata e 5 perfis sob campo cerrado nativo

Disclosing Hypoalbuminemia: A Lupus Protein-Losing Enteropathy (Lupple) Report

A enteropatia perdedora de proteínas (EPP) caracteriza-se pela presença de edema generalizado e hipoalbuminemia grave, secundários à perda proteica através do trato gastrointestinal. Os autores reportam um caso de enteropatia perdedora de proteínas secundária a lupus eritematoso sistémico (LES), como a manifestação inicial desta doença. A doente relatava um quadro pautado por 4 meses de diarreia aquosa, não sanguinolenta, (com um máximo de 10 dejeções diárias), e perda ponderal significativa. Posteriormente desenvolveu marcado edema periférico e rash cutâneo malar e maculopapular ao nível do tórax e membros. Analiticamente apresentava anemia, hipoalbuminemia grave, hipocaliémia e hipomagnesémia. No decurso da investigação foram excluídas proteinúria e outras causas de hipoalbuminemia. Após resultados como a pesquisa de anticorpos anti-nucleares e anti-ribonucleoproteinas positiva foi assumido o diagnóstico de EPP secundária ao LES. A doente foi tratada com pulsos de Metilprednisolona 1000 mg/dia durante 3 dias, seguido de prednisolona 1 mg/kg/dia, com boa resposta clínica. Após 20 dias, foi adicionada Azatioprina e iniciado o desmame de corticoides. O presente caso clínico destaca uma EPP como forma de apresentação do LES, cujo diagnóstico pode passar despercebido, tendo em conta a sua raridade, e acarretar um aumento da morbilidade e mortalidade.info:eu-repo/semantics/publishedVersio

Thermo-responsive microemulsions containing deep eutectic-based antibiotic formulations for improved treatment of resistant bacterial ocular infections

The rise of antibiotic resistant strains, as methicillin-resistant Staphylococcus aureus (MRSA), challenges the current treatment of infections. In the case of ocular infections, antibiotic eye drops are commonly prescribed. However, their efficacy is usually compromised by the low viscosity of these formulations and the eye drainage. To overcome these drawbacks, deep eutectic solvent (DES)-based microemulsions with thermo-responsive character, that increase their viscosity upon contact with the eye have been developed. Using betaine-based DES aqueous solutions, it is possible to increase up to 140-fold the water solubility of the antibiotic chloramphenicol, typically used in ocular infections. The DES solutions containing the antibiotic are applied as water phases in water-in-oil-in-water (w/o/w) microemulsions, being stable up to 3 months. Furthermore, a sustained-release and a higher permeation of the antibiotic through the cornea than that of commercialized eye drops is achieved, while presenting comparable cytotoxicity profiles (cell viabilities > 88%). Higher antimicrobial activity and faster action of the antibiotic in case of infection with MRSA is observed compared to the commercialized formulations (7 log10 of inactivation in 48 h vs 72 h). Overall, these microemulsions comprising DES are a promising strategy to achieve higher antibiotic effectiveness in the treatment of resistant bacterial infections.info:eu-repo/semantics/publishedVersio

Avaliação genómica nas espécies pecuárias

info:eu-repo/semantics/publishedVersio

"Sustainable Cellulose Nanofibers-Mediated Synthesis of Uniform Spinel Zn-Ferrites Nanocorals for High Performances in Supercapacitors"

Spinel ferrites are versatile, low-cost, and abundant metal oxides with remarkable electronic and magnetic properties, which find several applications. Among them, they have been considered part of the next generation of electrochemical energy storage materials due to their variable oxidation states, low environmental toxicity, and possible synthesis through simple green chemical processing. However, most traditional procedures lead to the formation of poorly controlled materials (in terms of size, shape, composition, and/or crystalline structure). Thus, we report herein a cellulose nanofibers-mediated green procedure to prepare controlled highly porous nanocorals comprised of spinel Zn-ferrites. Then, they presented remarkable applications as electrodes in supercapacitors, which were thoroughly and critically discussed. The spinel Zn-ferrites nanocorals supercapacitor showed a much higher maximum specific capacitance (2031.81 F g−1 at a current density of 1 A g−1) than Fe2O3 and ZnO counterparts prepared by a similar approach (189.74 and 24.39 F g−1 at a current density of 1 A g−1). Its cyclic stability was also scrutinized via galvanostatic charging/discharging and electrochemical impedance spectroscopy, indicating excellent long-term stability. In addition, we manufactured an asymmetric supercapacitor device, which offered a high energy density value of 18.1 Wh kg−1 at a power density of 2609.2 W kg−1 (at 1 A g−1 in 2.0 mol L−1 KOH electrolyte). Based on our findings, we believe that higher performances observed for spinel Zn-ferrites nanocorals could be explained by their unique crystal structure and electronic configuration based on crystal field stabilization energy, which provides an electrostatic repulsion between the d electrons and the p orbitals of the surrounding oxygen anions, creating a level of energy that determines their final supercapacitance then evidenced, which is a very interesting property that could be explored for the production of clean energy storage devices

Exploring the genetic origin of Brazilian locally adapted breeds: admixture, population history and relationship with Portuguese and indicine cattle.

The domestication of bovines has given rise to distinct phenotypes resulting in diverse breeds worldwide. Subsequent artificial selection has further enriched the complexity and diversity to cattle sub-species adapting them to their various purposes and evolving environment. Among these cattle sub-species, native Portuguese cattle breeds are considered a repository of biodiversity shaped by genetic and environmental effects accumulated over the years. In Brazil, taurine animals were introduced between the 16th and 17th centuries by the European conquerors to be used for food, leather, and animal traction. Through generations of casual crossings in diverse ecosystems, these animals became adapted to a wide range of environments and displaying varying levels of phenotypic variability and improved fitness to local conditions, hereafter recognized as Iberian-derived Locally Adapted breeds. Thus, we focused in assess 13 cattle breeds representing two geographic origins: Portuguese Iberian cattle and Brazilian Iberian-derived Locally Adapted breeds. The aim is to understand the genetic architecture of Brazilian Iberian-derived Locally Adapted breeds and their potential relationship with Portuguese Iberian cattle and Brazilian indicine breeds. In our study, we observed varying extents of linkage disequilibrium across the evaluated breeds, along with differences in effective population size. Runs of homozygosity analyses revealed different genes associated with common traits, even within a cluster group. For instance, genes related to immune response, such as MAVS (Mertolenga), DTX (Barrosa), ˜ ZBTB16 (Brava de Lide), DUSP22 (Pantaneiro), and IL7R (Caracu Dairy and Caracu Beef). Overall, our results highlight that both populations studied, with their specificities, are crucial sources of animal genetic resource of animal genetic resources for food and agriculture