American tegumentary leishmaniasis: epidemiological and molecular characterization of prevalent Leishmania species in the State of Tocantins, Brazil, 2011-2015

Determination of the epidemiological profile of the American tegumentary leishmaniasis (ATL) and identification of Leishmania species that are prevalent in the State of Tocantins were carried out through a retrospective and descriptive study based on data reported in SINAN, in the period from 2011 to 2015. Molecular techniques such as PCR-RFLP and PCR-G6PD to amplify Leishmania DNA were performed on stored on Giemsa-stained slides from lesion scarifications of ATL patients who were amastigote-positive by the direct microscopic examination. There were 1,434 ATL cases in Tocantins reported in this period. The highest incidence was reported in men aged over 60 years, rural residents, the most affected ethnic group was mixed ethnicity (mixed black and white) and the ones with lower education. The predominant clinical form was cutaneous, being diagnosed mainly by laboratory methods. Pentavalent antimonial was effective in resolving cases. The predominant species found in 271 analyzed samples from 32 municipalities located in 8 different health regions of Tocantins was Leishmania (Viannia) braziliensis. Identifying the epidemiological profile and characterizing the Leishmania spp species on regional level is essential to establish control and prevention behaviors, minimizing the number of cases and treatment resistance, recurrence and evolution to mucosal forms

Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation.

Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8-30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates

Eliciting reflections on caring theory in elderly caring practice

Caring theories are the description and conceptualization of the care that is given in caring practise by nurses and other professional caregivers with the aim of verbalizing and communicating caring phenomena. Intermittently, a theory –practice gap is given expression- that theory does not go along with clinical practice in caring

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Eye contact modulates facial mimicry in 4-month-old infants: an EMG and fNIRS study

Mimicry, the tendency to spontaneously and unconsciously copy others' behaviour, plays an important role in social interactions. It facilitates rapport between strangers, and is flexibly modulated by social signals, such as eye contact. However, little is known about the development of this phenomenon in infancy, and it is unknown whether mimicry is modulated by social signals from early in life. Here we addressed this question by presenting 4-month-old infants with videos of models performing facial actions (e.g., mouth opening, eyebrow raising) and hand actions (e.g., hand opening and closing, finger actions) accompanied by direct or averted gaze, while we measured their facial and hand muscle responses using electromyography to obtain an index of mimicry (Experiment 1). In Experiment 2 the infants observed the same stimuli while we used functional near-infrared spectroscopy to investigate the brain regions involved in modulating mimicry by eye contact. We found that 4-month-olds only showed evidence of mimicry when they observed facial actions accompanied by direct gaze. Experiment 2 suggests that this selective facial mimicry may have been associated with activation over posterior superior temporal sulcus. These findings provide the first demonstration of modulation of mimicry by social signals in young human infants, and suggest that mimicry plays an important role in social interactions from early in life. [Abstract copyright: Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Noble Metal Nanoparticles for Biosensing Applications

In the last decade the use of nanomaterials has been having a great impact in biosensing. In particular, the unique properties of noble metal nanoparticles have allowed for the development of new biosensing platforms with enhanced capabilities in the specific detection of bioanalytes. Noble metal nanoparticles show unique physicochemical properties (such as ease of functionalization via simple chemistry and high surface-to-volume ratios) that allied with their unique spectral and optical properties have prompted the development of a plethora of biosensing platforms. Additionally, they also provide an additional or enhanced layer of application for commonly used techniques, such as fluorescence, infrared and Raman spectroscopy. Herein we review the use of noble metal nanoparticles for biosensing strategies—from synthesis and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics laboratory

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Development of Improved Charcoal-Fueled Cookstove for Cooking Applications in Rural Households

<p>In the Philippines, charcoal is among the preferred fuel types used for residential cooking and water boiling applications. However, charcoal combustion emissions are known to contain compounds toxic to human health. It is estimated that millions of Filipinos residing in households that use charcoal for cooking and water boiling may be exposed to alarming concentrations of household air pollutants (HAP). Indoor exposure of residents is a function of many variables such as fuel combustion efficiency, fuel type, emission exhaust from the dwelling space, ventilation, and kitchen placement and orientation. The study focused on the development of an improved cookstove, the assessment of its performance, and the impact of its use on the exposure of a simulated occupant. A modified water boiling test was conducted, based on the protocol developed by the Global Alliance for Clean Cookstoves. Cookstove performance was quantified using the former's ready-made e-spreadsheet. HAP considered in the study were carbon monoxide, carbon dioxide, and both respirable and inhalable particulate matter. Physical conditions (dry bulb temperature and relative humidity) were also assessed.</p