Occurence and variability of norA and other main multidrug efflux pump determinants across the Staphylococcus genus

Background Multidrug efflux pumps (MDR EPs) play a major role in the emergence of antimicrobial resistance (AMR). NorA is one of the main native MDR EPs of Staphylococcus aureus, contributing to reduced susceptibility towards fluoroquinolones and biocides[1,2]. In S. aureus, its gene occurs in several allelic variants[3], but less is known about the occurrence of norA and other MDR EPs across the Staphylococcus genus. In this work, we analyze the presence of norA across staphylococci and identify other main MDR EP determinants in four additional pathogenic staphylococcal species. Methods The norA nucleotide sequences from 61 Staphylococcus species were retrieved from public databases and aligned. The corresponding predicted polypeptide sequences were also aligned and the impact of possible residue substitutions on NorA activity was analyzed. Other MDR EP genes were searched in public databases for Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdunensis and Staphylococcus hominis. Additionally, sequences homologues to S. aureus norB/C, sdrM, lmrS, mepA and mdeA were screened by BLAST search in the complete genome of representative strains of each species. Results The norA phylogenetic tree follows the evolutionary relations of the Staphylococcus genus highlighting the presence of norA in the early branching of the genus. Comparative analyses suggest a conservation of NorA function in staphylococci. Over 30 putative MDR EP genes were identified for S. epidermidis, S. haemolyticus and S. lugdunensis. Homologues of S. aureus norB/C and sdrM were identified in both S. epidermidis and S. hominis, while mepA and mdeA were only detected in S. hominis and lmrS in S. epidermidis. Conclusions Our results suggest an overall conservation of NorA function across staphylococci, indicating that norA is part of the staphylococcal core genome. The identification of main MDR EP determinants in other staphylococcal species of clinical relevance opens new avenues for the study of their impact on AMR. Project BIOSAFE funded by FEDER through the Programa Operacional Factores de Competitividade—COMPETE and by Fundação para a Ciência e a Tecnologia (FCT, Portugal)— Grants LISBOA-01-0145-FEDER-030713, PTDC/CAL-EST/30713/2017, 2021.05063.BD and UID/04413/2020publishe

Comorbidades associadas às epilepsias e cefaleias

Comorbidities are often associated with chronic neurological diseases, such as headache and epilepsy. OBJECTIVES: To identify comorbidities associated with epilepsy and headaches, and to determine possible drug interactions. METHODS: A standardized questionnaire with information about type of epilepsy/headache, medical history, and medication was administered to 80 adult subjects (40 with epilepsy and 40 with chronic headache). RESULTS: Patients with epilepsy had an average of two comorbidities and those with headache of three. For both groups, hypertension was the most prevalent. On average, patients with epilepsy were taking two antiepileptic medications and those with headache were taking only one prophylactic medication. Regarding concomitant medications, patients with epilepsy were in use, on average, of one drug and patients with headache of two. CONCLUSIONS: Patients with chronic neurological diseases, such as epilepsy and headaches, have a high number of comorbidities and they use many medications. This may contribute to poor adherence and interactions between different medications.As comorbidades geralmente estão associadas a doenças neurológicas crônicas, tais como cefaleia e epilepsia. OBJETIVOS: Identificar comorbidades associadas à epilepsia e cefaleia e determinar as possíveis interações de drogas. MÉTODOS: Questionário padronizado com informações sobre o tipo de epilepsia/cefaleia, os antecedentes médicos e as medicações foi aplicado a 80 indivíduos adultos (40 com epilepsia e 40 com cefaleia crônica). RESULTADOS: Pacientes com epilepsia e cefaleia apresentaram uma média de duas e três comorbidades, respectivamente, sendo, para ambos, hipertensão arterial sistêmica a mais prevalente. Em média, os pacientes com epilepsia estavam em uso de duas medicações antiepilépticas; aqueles com cefaleia, uma medicação profilática. Em relação às medicações concomitantes, os pacientes com epilepsia estavam em uso, em média, de uma droga e os pacientes com cefaleia de duas. CONCLUSÕES: Pacientes com doenças neurológicas crônicas, como epilepsia e cefaleia, apresentam elevado número de comorbidades e utilizam grande número de medicações. Isso pode contribuir para diminuir a aderência ao tratamento e facilitar interações entre diversas medicações.27427

Enterobius vermicularis: Ancient DNA from North and South American Coprolites

A molecular paleoparasitological diagnostic approach was developed for Enterobius vermicularis. Ancient DNA was extracted from 27 coprolites from archaeological sites in Chile and USA. Enzymatic amplification of human mtDNA sequences confirmed the human origin. We designed primers specific to the E. vermicularis 5S ribosomal RNA spacer region and they allowed reproducible polymerase chain reaction identification of ancient material. We suggested that the paleoparasitological microscopic identification could accompany molecular diagnosis, which also opens the possibility of sequence analysis to understand parasite-host evolution

Dehydropeptide supramolecular hydrogels and nanostructures as potential peptidomimetic biomedical materials

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019). FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowledged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015)

Social capital and self-rated health among adolescents in Brazil: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Social capital may influence health and the patterns of association differ according its dimension such as cognitive, behavioral, bridging or bonding. There is a few numbers of studies in Latin America which comprise these aspects of social capital and health. The aim of this study was to examine the association between social capital and self-rated health among youth, and distinguish between the different forms of social capital - cognitive versus behavioral, and bonding versus bridging.</p> <p>Findings</p> <p>A cross-sectional study was conducted in 2009 among working adolescents supported by a Brazilian NGO. The sample comprised 363 individuals and data were collected using a validated structured questionnaire. The outcome, self-rated health, was measured as a dichotomous variable (poor/good health) and fourteen social capital indicators were investigated (cognitive, behavioral and bonding/bridging). Data were analyzed using multivariate logistic regression. Cognitive (social support and trust), behavioral (civic participation) and bridging social capital were associated with good self-rated health after adjustment of all the other social capital indicators and confounders (sex, age, skin color and educational background).</p> <p>Conclusions</p> <p>Social capital was associated with self-rated health and the patterns of association differed according its specific dimensions. Cognitive, behavioral and bridging social capitals were protective for adolescents health living in a developing country context..</p

Design and calibration of reference leaks

Funding Information: This work was supported by the Joint Research Project (JRP) 20IND10 «Metrology for decarbonising the gas grid» (Decarb) funded by the European Metrology Programme for Innovation and Research (EMPIR). The EMPIR initiative is co-funded by the European Union's Horizon 2020 research and innovation programme and the EMPIR Participating States. Publisher Copyright: © 2024The introduction of hydrogen into the gas grid requires stricter safety measures due to its enhanced flammability compared to natural gas. Detecting small hydrogen leaks is crucial for meeting health and safety requirements, given hydrogen's potential for easy ignition and the hazards associated with its combustion. This paper presents an overview of the quantification of small hydrogen leaks, regarding conversions between common units of measurement, namely concentration and leak rate. In addition, the need for traceable assessments of hydrogen leakage was also considered, which included proposal of the design, calibration, and metrological evaluation of portable hydrogen reference leaks in the range of 10−6 to 10−4 Std cm3/s, the latter being considered as the lowest side of the range of interest for quantifying hydrogen leaks. Two methods of manufacturing leak artefacts, namely conductance and permeation, are explored, and the produced leaks were used to test two hydrogen leak detectors with different working principles. A calibration technique based on a constant pressure gas flowmeter is described together with the uncertainty budget. The study provides insights into the challenges of calibrating detectors for hydrogen leaks, highlighting the importance of traceability in ensuring safety and environmental protection in the context of hydrogen infrastructure. It was demonstrated that reference leaks are highly suitable to test hydrogen leak detectors in the mentioned flow range due to their simplicity, high reliability, low depletion rate and high portability.publishersversionpublishe

Transcriptome analysis of Taenia solium cysticerci using Open reading Frame ESTS (ORESTES)

<p>Abstract</p> <p>Background</p> <p>Human infection by the pork tapeworm <it>Taenia solium </it>affects more than 50 million people worldwide, particularly in underdeveloped and developing countries. Cysticercosis which arises from larval encystation can be life threatening and difficult to treat. Here, we investigate for the first time the transcriptome of the clinically relevant cysticerci larval form.</p> <p>Results</p> <p>Using Expressed Sequence Tags (ESTs) produced by the ORESTES method, a total of 1,520 high quality ESTs were generated from 20 ORESTES cDNA mini-libraries and its analysis revealed fragments of genes with promising applications including 51 ESTs matching antigens previously described in other species, as well as 113 sequences representing proteins with potential extracellular localization, with obvious applications for immune-diagnosis or vaccine development.</p> <p>Conclusion</p> <p>The set of sequences described here will contribute to deciphering the expression profile of this important parasite and will be informative for the genome assembly and annotation, as well as for studies of intra- and inter-specific sequence variability. Genes of interest for developing new diagnostic and therapeutic tools are described and discussed.</p

Potential of mannan or dextrin nanogels as vaccine carrier/adjuvant systems

Polymeric nanogels have been sophisticatedly designed promising a new generation of vaccine delivery/adjuvant systems capable of boosting immune response, a strategic priority in vaccine design. Here, nanogels made of mannan or dextrin were evaluated for their potential as carriers/adjuvants in vaccine formulations. Since lymph nodes are preferential target organs for vaccine delivery systems, nanogels were biotin-labeled, injected in the footpad of rats, and their presence in draining lymph nodes was assessed by immunofluorescence. Nanogels were detected in the popliteal and inguinal lymph nodes by 24h upon subcutaneous administration, indicating entrapment in lymphatic organs. Moreover, the model antigen ovalbumin was physically encapsulated within nanogels and physicochemically characterized concerning size, zeta potential, ovalbumin loading, and entrapment efficiency. The immunogenicity of these formulations was assessed in mice intradermally immunized with ovalbuminmannan or ovalbumindextrin by determining ovalbumin-specific antibody serum titers. Intradermal vaccination using ovalbuminmannan elicited a humoral immune response in which ovalbumin-specific IgG1 levels were significantly higher than those obtained with ovalbumin alone, indicating a TH2-type response. In contrast, dextrin nanogel did not show adjuvant potential. Altogether, these results indicate that mannan nanogel is a material that should be explored as a future antigen delivery system.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported by the Fundação para a Ciência e a Tecnologia (FCT) Portugal, post-doc grant SFRH/BPD/70524/2010 and the International Iberian Nanotechnology Laboratory (INL), PhD grant. The authors thank the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). The authors also acknowledge the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462)

Paleoparasitology: Perspectives with New Techniques

Paleoparasitology is the study of parasites found in archaeological material. The development of this field of research began with histological identification of helminth eggs in mummy tissues, analysis of coprolites, and recently through molecular biology. An approach to the history of paleoparasitology is reviewed in this paper, with special reference to the studies of ancient DNA identified in archaeological material. Paleoparasitologia: perspectivas com novas técnicas Paleoparasitologia é o estudo de parasitos encontrados em material arqueológico. O desenvolvimento deste campo da pesquisa teve início com a identificação de ovos de helmintos em tecidos mumificados, análise de coprólitos e, recentemente, através da biologia molecular. Neste artigo faz-se uma breve revisão da história da paleoparasitologia com referência especial aos estudos de ADN antigo (ancient DNA) em material arqueológic

Paleoparasitology: Perspectives with New Techniques

Paleoparasitology is the study of parasites found in archaeological material. The development of this field of research began with histological identification of helminth eggs in mummy tissues, analysis of coprolites, and recently through molecular biology. An approach to the history of paleoparasitology is reviewed in this paper, with special reference to the studies of ancient DNA identified in archaeological material. Paleoparasitologia: perspectivas com novas técnicas Paleoparasitologia é o estudo de parasitos encontrados em material arqueológico. O desenvolvimento deste campo da pesquisa teve início com a identificação de ovos de helmintos em tecidos mumificados, análise de coprólitos e, recentemente, através da biologia molecular. Neste artigo faz-se uma breve revisão da história da paleoparasitologia com referência especial aos estudos de ADN antigo (ancient DNA) em material arqueológic