Effects of CPAP on nitrate and norepinephrine levels in severe and mild-moderate sleep apnea

Background: Reduced plasma nitrate (NOx) levels and increased urinary norepinephrine (U-NE) levels have been described in severe obstructive sleep apnea (OSA), and are reverted by continuous positive airway pressure (CPAP). The effect of CPAP on these biomarkers in mild-moderate OSA is not well understood. The aim of this study was to compare NOx and U-NE levels and blood pressure (BP) between male patients with mild-moderate and severe OSA and determine the impact of 1 month of CPAP therapy on these parameters. Methods: We undertook a prospective study of 67 consecutive OSA patients (36 mild-moderate, 31 severe). Measurements of plasma NOx at 11 pm, 4 am and 7 am, 24-h U-NE and ambulatory BP were obtained at baseline and after 1 month of CPAP. Results: At baseline, NOx levels showed a significant decrease during the night in both groups (p < 0.001). U-NE level and BP were significantly higher in the severe OSA group. After 1 month of CPAP, there was a significant increase in NOx levels and a reduction in U-NE level and BP only in patients with severe OSA. Conclusions: One month of CPAP results in significant improvements in NOx levels, 24-h U-NE level and BP in patients with severe OSA, but not in patients with mild-moderate OSA.publishersversionpublishe

Novel and revisited approaches in nanoparticle systems for buccal drug delivery

The buccal route is considered patient friendly due to its non-invasive nature and ease of administration. Such delivery route has been used as an alternative for the delivery of drugs that undergo first-pass metabolism or are susceptible to pH and enzymatic degradation, such as occurs in the gastrointestinal tract. However, the drug concentration absorbed in the buccal mucosa is often low to obtain an acceptable therapeutic effect, mainly due to the saliva turnover, tongue and masticatory movements, phonation, enzymatic degradation and lack of epithelium permeation. Therefore, the encapsulation of drugs into nanoparticles is an important strategy to avoid such problems and improve their buccal delivery. Different materials from lipids to natural or synthetic polymers and others have been used to protect and deliver drugs in a sustained, controlled or targeted manner, and enhance their uptake through the buccal mucosa improving their bioavailability and therapeutic outcome. Overall, the main aim of this review is to perform an overview about the nanotechnological approaches developed so far to improve the buccal delivery of drugs. Herein, several types of nanoparticles and delivery strategies are addressed, and a special focus on pipeline products is also given.info:eu-repo/semantics/acceptedVersio

Live neighbor-joining

Background: In phylogenetic reconstruction the result is a tree where all taxa are leaves and internal nodes are hypothetical ancestors. In a live phylogeny, both ancestral and living taxa may coexist, leading to a tree where internal nodes may be living taxa. The well-known Neighbor-Joining heuristic is largely used for phylogenetic reconstruction. Results: We present Live Neighbor-Joining, a heuristic for building a live phylogeny. We have investigated Live Neighbor-Joining on datasets of viral genomes, a plausible scenario for its application, which allowed the construction of alternative hypothesis for the relationships among virus that embrace both ancestral and descending taxa. We also applied Live Neighbor-Joining on a set of bacterial genomes and to sets of images and texts. Non-biological data may be better explored visually when their relationship in terms of content similarity is represented by means of a phylogeny. Conclusion: Our experiments have shown interesting alternative phylogenetic hypothesis for RNA virus genomes, bacterial genomes and alternative relationships among images and texts, illustrating a wide range of scenarios where Live Neighbor-Joining may be used

A method to find groups of orthogous genes across multiple genomes

In this work we propose a simple method to obtain groups of homologous genes across multiple (k) organisms, called kGC. Our method takes as input all-against-all Blastp comparisons and produces groups of homologous sequences. First, homologies among groups of paralogs of all the k compared genomes are found, followed by homologies of groups among k - 1 genomes and so on, until groups belonging exclusively to only one genome, that is, groups of one genome not presenting strong similarities with any group of any other genome, are identified. We have used our method to determine homologous groups across six Actinobacterial complete genomes. To validate kGC, we first investigate the Pfam classification of the homologous groups, and after compare our results with those produced by OrthoMCL. Although kGC is much simpler than OrthoMCL it presented similar results with respect to Pfam classification

Corrosion and tribocorrosion behaviour of Ti6Al4V produced by selective laser melting and hot pressing in comparison with the commercial alloy

The corrosion and tribocorrosion behaviour of SLM-produced Ti6Al4V alloy was studied in comparison with its HP and commercial counterparts in 9 g/L NaClsolution at body temperature. Results showed that SLM processing route influenced the electrochemical response of the SLM-produced alloy by leading to a relatively lower quality for the passive film due to decreased beta phase and the formation of alpha' phase. However, after tribocorrosion, neither the total volume loss nor the volume loss under the influence of mechanical wear and wear accelerated corrosion showed any statistically significant difference between the processing routes.This study was supported by FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 - Program Operacional Competitividade e Internacionalizacao (POCI) with the reference project POCI-01-0145-FEDER-006941, together with projects NORTE-01-0145-FEDER-000018-HAMaBICo and PTDC/EMS-TEC/5422/2014. The authors would also like to acknowledge Prof. Grata Minas for the provision of the profilometry

Towards a structural understanding of the fibrillization pathway in Machado-Joseph’s disease: trapping early oligomers of non-expanded ataxin-3

Machado-Joseph’s disease is caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract in the protein ataxin-3. Except for the polyglutamine region, proteins associated with polyglutamine diseases are unrelated, and for all of these diseases aggregates containing these proteins are the major components of the nuclear proteinaceous deposits found in the brain. Aggregates of the expanded proteins display amyloid-like morphological and biophysical properties. Human ataxin-3 containing a non-pathological number of glutamine residues (14Q), as well as its Caenorhabditis elegans (1Q) orthologue, showed a high tendency towards self-interaction and aggregation, under nearphysiological conditions. In order to understand the discrete steps in the assembly process leading to ataxin-3 oligomerization, we have separated chromatographically high molecular mass oligomers as well as medium mass multimers of non-expanded ataxin-3. We show that: (a) oligomerization occurs independently of the poly(Q)-repeat and it is accompanied by an increase in b-structure; and (b) the first intermediate in the oligomerization pathway is a Josephin domain-mediated dimer of ataxin- 3. Furthermore, non-expanded ataxin-3 oligomers are recognized by a specific antibody that targets a conformational epitope present in soluble cytotoxic species found in the fibrillization pathway of expanded polyglutamine proteins and other amyloid-forming proteins. Imaging of the oligomeric forms of the non-pathological protein using electron microscopy reveals globular particles, as well as short chains of such particles that likely mimic the initial stages in the fibrillogenesis pathway occurring in the polyglutamine-expanded protein. Thus, they constitute potential targets for therapeutic approaches in Machado-Joseph’s disease, as well as valuable diagnostic markers in disease settings