Toxicological evaluation of lactose and chitosan delivered by inhalation

These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione ( GSSG), myeloperoxidase ( MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 ( P = 0.011) for MPO and 0.89 +/- 0.68 versus 2.02 +/- 0.22 ( P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators

Ocean Acidification Disrupts Prey Responses to Predator Cues but Not Net Prey Shell Growth in Concholepas concholepas (loco)

Background Most research on Ocean Acidification (OA) has largely focused on the process of calcification and the physiological trade-offs employed by calcifying organisms to support the building of calcium carbonate structures. However, there is growing evidence that OA can also impact upon other key biological processes such as survival, growth and behaviour. On wave-swept rocky shores the ability of gastropods to self-right after dislodgement, and rapidly return to normal orientation, reduces the risk of predation. Methodology/Principal Findings The impacts of OA on this self-righting behaviour and other important parameters such as growth, survival, shell dissolution and shell deposition in Concholepas concholepas (loco) were investigated under contrasting pCO2 levels. Although no impacts of OA on either growth or net shell calcification were found, the results did show that OA can significantly affect self-righting behaviour during the early ontogeny of this species with significantly faster righting times recorded for individuals of C. concholepas reared under increased average pCO2 concentrations (± SE) (716±12 and 1036±14 µatm CO2) compared to those reared at concentrations equivalent to those presently found in the surface ocean (388±8 µatm CO2). When loco were also exposed to the predatory crab Acanthocyclus hassleri, righting times were again increased by exposure to elevated CO2, although self-righting times were generally twice as fast as those observed in the absence of the crab. Conclusions and Significance These results suggest that self-righting in the early ontogeny of C. concholepas will be positively affected by pCO2 levels expected by the end of the 21st century and beginning of the next one. However, as the rate of self-righting is an adaptive trait evolved to reduce lethal predatory attacks, our result also suggest that OA may disrupt prey responses to predators in nature

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

Tailoring r-index for Document Listing Towards Metagenomics Applications

A basic problem in metagenomics is to assign a sequenced read to the correct species in the reference collection. In typical applications in genomic epidemiology and viral metagenomics the reference collection consists of a set of species with each species represented by its highly similar strains. It has been recently shown that accurate read assignment can be achieved with k-mer hashing-based pseudoalignment: a read is assigned to species A if each of its k-mer hits to a reference collection is located only on strains of A. We study the underlying primitives required in pseudoalignment and related tasks. We propose three space-efficient solutions building upon the document listing with frequencies problem. All the solutions use an r-index (Gagie et al., SODA 2018) as an underlying index structure for the text obtained as concatenation of the set of species, as well as for each species. Given t species whose concatenation length is n, and whose Burrows-Wheeler transform contains r runs, our first solution, based on a grammar-compressed document array with precomputed queries at non terminal symbols, reports the frequencies for the distinct documents in which the pattern of length m occurs in time. Our second solution is also based on a grammar-compressed document array, but enhanced with bitvectors and reports the frequencies in time, over a machine with wordsize w. Our third solution, based on the interleaved LCP array, answers the same query in time. We implemented our solutions and tested them on real-world and synthetic datasets. The results show that all the solutions are fast on highly-repetitive data, and the size overhead introduced by the indexes are comparable with the size of the r-index.Peer reviewe

Design and validation of the INCUE questionnaire: Assessment of primary healthcare Nurses’ basic training needs in palliative care

Many instruments have been created to measure knowledge and attitudes in palliative care. However, not only is it important to acquire knowledge, but also that this knowledge should reach patients and their relatives through application in clinical practice. This study aimed to develop and psychometrically test the INCUE questionnaire (Investigación Cuidados Enfermeros/Investigation into Nurses’ Care Understanding of End-of-Life) to assess the basic training needs of primary or home healthcare nurses in palliative care. A questionnaire was developed based on the classical theory of tests and factor analysis models. Initially, 18 experts developed 67 items in two blocks and determined content validity by two rounds of expert panels. Exploratory factor analysis and reliability testing were conducted with a non-probabilistic sample of 370 nurses. Some items were observed to have very low homogeneity indices or presented convergence problems and were eliminated. Questionnaire reliability was 0.700 in the theoretical block (KR20 Index) and 0.941 in the practical block (Cronbach’s alpha). The model converges and shows an adequate fit, specifically CFI = 0.977, TLI = 0.977 and RMSEA = 0.05. The correlation between the two factors in the model is ρ = 0.63. The questionnaire objectively evaluates primary or home healthcare nurses’ knowledge of palliative care and its practical application, thereby facilitating more efficient training plans.This questionnaire is being developed as part of a project to pinpoint the training needs of primary care nurses in the field of palliative care at the Dr Peset Health Department in Valencia (Project EAPCP19-V01)This project has received funding under the first Call for R + D Grants in Nursing 2019 (UGP-19-258), from the Fundació per al Foment de la Investigació Sanitària i Bioèdica de la Comunitat Valenciana (Fisabio).Enfermerí

Pruning Algorithms for Low-Dimensional Non-metric k-NN Search: A Case Study

We focus on low-dimensional non-metric search, where tree-based approaches permit efficient and accurate retrieval while having short indexing time. These methods rely on space partitioning and require a pruning rule to avoid visiting unpromising parts. We consider two known data-driven approaches to extend these rules to non-metric spaces: TriGen and a piece-wise linear approximation of the pruning rule. We propose and evaluate two adaptations of TriGen to non-symmetric similarities (TriGen does not support non-symmetric distances). We also evaluate a hybrid of TriGen and the piece-wise linear approximation pruning. We find that this hybrid approach is often more effective than either of the pruning rules. We make our software publicly available

Exclusive neuronal expression of SUCLA2 in the human brain

SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex

Fibrin Sealants and Axillary Lymphatic Morbidity. A Systematic Review and Meta-Analysis of 23 Clinical Randomized Trials

Background: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenec- tomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. Methods: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. Results: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin’s disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). Conclusion: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found

Illusory vowels in Spanish-English sequential bilinguals: Evidence that accurate L2 perception is neither necessary nor sufficient for accurate L2 production

Spanish native speakers are known to pronounce onset /sC/ clusters in English with a prothetic vowel, as in esport for sport, due to their native language phonotactic constraints. We assessed whether accurate production of e.g. spi instead of espi was related to accurate perceptual discrimination of this contrast in second language (L2) speech of Spanish–English sequential bilinguals. A same–different discrimination task in stimulus pairs such as spi–espi assessed speech perception and a phonemic verbal fluency task elicited speech production. Logistic mixed model regressions revealed significant differences in accuracy between the bilinguals and the English monolinguals, although some bilinguals performed within the monolingual range. For the production task, but not for the perception task, bilinguals with more exposure to English and greater grammatical knowledge of English performed significantly more accurately than those with less exposure and lower grammatical knowledge. There was no significant correlation between production accuracy and perception accuracy. Through examining phonotactic constraints, these results expand a growing body of research into single sounds which suggests dissociations between L2 perception and production. In contrast to predictions made by L2 speech models, the findings indicate that accurate L2 perception is neither necessary nor sufficient for accurate L2 production, and instead are interpreted to indicate that the two capacities recruit different executive control mechanisms and are acquired – at least to a certain extent – independently in L2 acquisition.Peer Reviewe