Design and Synthesis of a New Class of Twin-Chain Amphiphiles for Self-Assembled Monolayer-based Electrochemical Biosensor Applications

A new class of twin-chain hydroxyalkylthiols (mercaptoalkanols) featuring a nearly constant cross-section and the potential for modification of one or both termini are available with complete regioselectivity through Pd-mediated couplings of benzene diiododitriflate, including an example of a previously unreported coupling to generate an ortho-substituted arene bis acetic acid. Selfassembled monolayers (SAMs) prepared from the new amphiphiles demonstrate improved stability in an electrochemical sensor system compared with monolayers prepared from analogous single chain thiols

Highly efficient t2 cobalt ferrite nanoparticles vectorized for internalization in cancer cells

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in the structure. A stable and biocompatible targeting conjugate nanoparticle-folic acid (NP-FA) was developed that was capable of targeting FA receptor positivity in HeLa (human cervical cancer) cancer cells. The biocompatibility of NP-FA was assessed in vitro in HeLa cells using the MTT assay, and morphological analysis of the cytoskeleton was performed. A high level of NP-FA binding to HeLa cells was confirmed through qualitative in vitro targeting studies. A value of 479 Fe+Co mM-1s-1 of transverse relaxivity (r2 ) was obtained in colloidal suspension. In addition, in vitro analysis in HeLa cells also showed an important effect in negative T2 contrast. Therefore, the results show that NP-FA can be a potential biomaterial for use in bio medical trials, especially as a contrast agent in magnetic resonance imaging (MRI)

Predominant factors of institutionalization in the elderly: a comparative study between home nursing and community dwelling

Purpose: The purpose of this paper was to detect the most significant factors associated with each living alternative to improve socialization and mental health of the elderly. The measurements included affective evaluation, cognitive assessment, anxiety level, physical functionality, quality of life and social relationships. Individuals in home nursing residences were older and had worse affective status, functionality, cognitive state and quality of life. Social relationships in community people were better than in the institutionalized condition, particularly for less aged people. Design/methodology/approach: Comparative descriptive study realized in 200 people older than 70 years in home nursing placement versus community dwelling conditions. Findings: Multivariate analysis and logistic regression indicated that greater disability and poorer quality of social relationships were the main factors influencing the institutionalization process. Specifically, the Sociotype Questionnaire appeared as an efficient tool concerning the detection of social isolation effects as well as an acceptable integrator of prosocial information about home nursing placement. Originality/value: The Geriatric Sociotype survey has shown usefulness in the evaluation of the social network of elderly people, both from the point of view of assessment and prognosis. In this sense it is considered that one of the main contributions of this study is to have included the qualitative evaluation of social relations, and to observe the differences according to the place of residence

Design and Synthesis of a New Class of Twin-Chain Amphiphiles for Self-Assembled Monolayer-based Electrochemical Biosensor Applications

A new class of twin-chain hydroxyalkylthiols (mercaptoalkanols) featuring a nearly constant cross-section and the potential for modification of one or both termini are available with complete regioselectivity through Pd-mediated couplings of benzene diiododitriflate, including an example of a previously unreported coupling to generate an ortho-substituted arene bis acetic acid. Selfassembled monolayers (SAMs) prepared from the new amphiphiles demonstrate improved stability in an electrochemical sensor system compared with monolayers prepared from analogous single chain thiols

Exploring the accessibility of deformed digital heritage models

The concept of accessibility has been examined by the scientific community in various fields such as education, health care, social inclusion, disabilities, transport, and tourism. Regarding heritage, the European Commission’s efforts toward accessible cultural heritage are highlighted, along with the use of digitisation and modelling technologies for complex heritage shapes. Thus, this chapter explores relevant scientific research into the accessibility of digital heritage models that represent the assets’ real condition, that is, as-is or as-built models produced using advanced digitisation and modelling technologies. The study emphasises the importance of both physical and semantic aspects of heritage conservation and the need for public awareness and cooperation toward the aimed accessibility. The methodology addresses the search for publications in Scopus and Web of Science and their filtering based on inclusion and exclusion criteria to ensure documents related to the accessibility of deformed digital heritage models are considered. The research concludes that creating accessible deformed digital heritage models is crucial for inclusion and participation from the public and stakeholders, and while some studies achieve accurate as-built geometries and accessibility, there is room for improvement

Rituximab versus tocilizumab and B-cell status in TNF-alpha inadequate-responder rheumatoid arthritis patients: the R4-RA RCT

BackgroundAlthough biological therapies have transformed the outlook for those with rheumatoid arthritis, there is a lack of any meaningful response in approximately 40% of patients. The role of B cells in rheumatoid arthritis pathogenesis is well recognised and is supported by the clinical efficacy of the B-cell-depleting agent rituximab (MabThera, F. Hoffman La-Roche Ltd, Basel, Switzerland). Rituximab is licensed for use in rheumatoid arthritis following failure of conventional synthetic disease-modifying antirheumatic drugs and tumour necrosis factor inhibitor therapy. However, over 50% of patients show low/absent synovial B-cell infiltration, suggesting that, in these patients, inflammation is driven by alternative cell types. This prompted us to test the hypothesis that, in synovial biopsy B-cell-poor patients, tocilizumab (RoActemra, F. Hoffman La-Roche Ltd, Basel, Switzerland) (targeting interleukin 6) is superior to rituximab (targeting CD20+/B cells).DesignThe R4–RA (A Randomised, open-labelled study in anti-TNFalpha inadequate responders to investigate the mechanisms for Response, Resistance to Rituximab versus Tocilizumab in Rheumatoid Arthritis patients) trial is a 48-week Phase IV, open-label, randomised controlled trial conducted in 19 European centres that recruited patients failing on or intolerant to conventional synthetic disease-modifying antirheumatic drug therapy and at least one tumour necrosis factor inhibitor.ParticipantsSynovial tissue was obtained at trial entry and classified histologically as B-cell rich or B-cell poor to inform balanced stratification. Patients were randomised on a 1 : 1 basis to receive standard therapy with rituximab or tocilizumab. B-cell-poor/-rich molecular classification was also carried out. The study was powered to test the superiority of tocilizumab over rituximab at 16 weeks in the B-cell-poor population.Main outcome measuresThe primary end point was defined as an improvement in the Clinical Disease Activity Index (CDAI) score of ≥ 50% from baseline. In addition, patients were considered to be non-responders if they did not reach an improvement in CDAI score of ≥ 50% and a CDAI score of ResultsIn total, 164 patients were randomised: 83 patients received rituximab and 81 received tocilizumab. Eighty-one out of 83 rituximab patients and 73 out of 81 tocilizumab patients completed treatment up to week 16 (primary end point). Baseline characteristics were comparable between the treatment groups. In the histologically classified B-cell-poor population (n = 79), no significant difference was observed in the primary outcome, an improvement in CDAI score of ≥ 50% from baseline (risk ratio 1.25, 95% confidence interval 0.80 to 1.96). A supplementary analysis of the CDAI-MTR, however, did reach statistical significance (risk ratio 1.96, 95% confidence interval 1.01 to 3.78). In addition, when B-cell-poor classification was determined molecularly, both the primary end point and the CDAI-MTR were statistically significant (risk ratio 1.72, 95% confidence interval 1.02 to 2.91, and risk ratio 4.12, 95% confidence interval 1.55 to 11.01, respectively). Moreover, a larger number of secondary end points achieved significance when classified molecularly than when classified histologically. In the B-cell-rich population, there was no significant difference between treatments in the majority of both primary and secondary end points. There were more adverse events and serious adverse events, such as infections, in the tocilizumab group than in the rituximab group.ConclusionTo our knowledge, this is the first biopsy-based, multicentre, randomised controlled trial of rheumatoid arthritis. We were unable to demonstrate that tocilizumab was more effective than rituximab in patients with a B-cell-poor pathotype in our primary analysis. However, superiority was shown in most of the supplementary and secondary analyses using a molecular classification. These analyses overcame possible unavoidable weaknesses in our original study plan, in which the histological method of determining B-cell status may have misclassified some participants and our chosen primary outcome was insufficiently sensitive. Given the significant results observed using the molecular classification, future research will focus on refining this stratification method and evaluating its clinical utility.Trial registrationCurrent Controlled Trials ISRCTN97443826.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 7. See the NIHR Journals Library website for further project information

Evaluating standards of care in psoriatic arthritis of the QUANTUM project (qualitative initiative to improve outcomes): results of an accreditation project in Spain

In Spain, the QUANTUM project has been promoted to reduce variability in clinical practice and improve the care and quality of life of people with psoriatic arthritis (PsA) by accrediting PsA units throughout the Spanish national health system. To present the results of this approach which sought to ensure an optimum level of quality for patients with PsA. Descriptive analysis of the self-assessments that the PsA units have carried out assessing their degree of compliance with the quality standards established in the QUANTUM project grouped into four blocks: shortening time to diagnosis; optimizing disease management; improving multidisciplinary collaboration; and improving patient monitoring. A total of 41 PsA units were self-evaluated. They met 64.1% of the defined quality standards. Optimize disease management obtained a higher level of standards compliance (72%) and improve multidisciplinary collaboration the lesser (63.9%). Accessibility to the treatments available for PsA in all hospitals was guaranteed (100%). Appropriate diagnostic equipment is available (97.6%). Compliance with specific quality standards leads to detect actions that should be implemented: quality of life assessment (9.8%), locomotor system assessment (12.2%), physical examination data record (14.6%), periodic cardiovascular risk assessment (17.1%). The QUANTUM project results make it possible to visualise how to care for patients with PsA is being developed in Spain. Problems identified in recent multinational reports are also identified in Spain

Gas exchange at whole plant level shows that a less conservative water use is linked to a higher performance in three ecologically distinct pine species

Increasing temperatures and decreasing precipitation in large areas of the planet as a consequence of global warming will affect plant growth and survival. However, the impact of climatic conditions will differ across species depending on their stomatal response to increasing aridity, as this will ultimately affect the balance between carbon assimilation and water loss. In this study, we monitored gas exchange, growth and survival in saplings of three widely distributed European pine species (Pinus halepensis, P. nigra and P. sylvestris) with contrasting distribution and ecological requirements in order to ascertain the relationship between stomatal control and plant performance. The experiment was conducted in a common garden environment resembling rainfall and temperature conditions that two of the three species are expected to encounter in the near future. In addition, gas exchange was monitored both at the leaf and at the whole-plant level using a transient-state closed chamber, which allowed us to model the response of the whole plant to increased air evaporative demand (AED). P. sylvestris was the species with lowest survival and performance. By contrast, P. halepensis showed no mortality, much higher growth (two orders of magnitude), carbon assimilation (ca. 14 fold higher) and stomatal conductance and water transpiration (ca. 4 fold higher) than the other two species. As a consequence, P. halepensis exhibited higher values of water-use efficiency than the rest of the species even at the highest values of AED. Overall, the results strongly support that the weaker stomatal control of P. halepensis, which is linked to lower stem water potential, enabled this species to maximize carbon uptake under drought stress and ultimately outperform the more water conservative P. nigra and P. sylvestris. These results suggest that under a hotter drought scenario P. nigra and P. sylvestris would very likely suffer increased mortality, whereas P. halepensis could maintain gas exchange and avoid water-induced growth limitation. This might ultimately foster an expansion of P. halepensis to higher latitudes and elevations.This work was supported by the projects ECOLPIN (AGL2011–24296) and Remedinal 3 (S2013/ MAE- 2719) of the Madrid Government, by a FPU fellowship from the Spanish Ministry of Education, Culture and Sport (FPU13/03410) to DS and by EU Marie Curie (FP7–2013-IOF-625988) fellowship to EPSC

Cardiovascular disease in immune-mediated inflammatory diseases: a cross-sectional analysis of 6 cohorts

Observational study[Abstract] To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis.We included 9951 patients. For each IMID, traditional cardiovascular risk factors had a different contribution to CVD. Overall, older age, longer disease duration, presence of traditional cardiovascular risk factors, and male sex were independently associated with a higher CVD prevalence. After adjusting for demographic and traditional cardiovascular risk factors, systemic lupus erythematosus exhibited the highest CVD standardized prevalence, followed by rheumatoid arthritis, psoriasis, Crohn disease, psoriatic arthritis, and ulcerative colitis (4.5 [95% confidence interval (CI): 2.2, 6.8], 1.3 [95% CI: 0.8, 1.8], 0.9 [95% CI: 0.5, 1.2], 0.8 [95% CI: 0.2, 1.3], 0.6 [95% CI: 0.2, 1.0], and 0.5 [95% CI: 0.1, 0.8], respectively).Systemic lupus erythematosus, rheumatoid arthritis, and psoriasis are associated with higher prevalence of CVD compared with other IMIDs. Specific prevention programs should be established in subjects affected with these conditions to prevent CVD

Atmospheric turbulence triggers pronounced diel pattern in karst carbonate geochemistry

CO2 exchange between terrestrial ecosystems and the atmosphere is key to understanding the feedbacks between climate change and the land surface. In regions with carbonaceous parent material, CO2 exchange patterns occur that cannot be explained by biological processes, such as disproportionate outgassing during the daytime or nighttime CO2 uptake during periods when all vegetation is senescent. Neither of these phenomena can be attributed to carbonate weathering reactions, since their CO2 exchange rates are too small. Soil ventilation induced by high atmospheric turbulence is found to explain atypical CO2 exchange between carbonaceous systems and the atmosphere. However, by strongly altering subsurface CO2 concentrations, ventilation can be expected to influence carbonate weathering rates. By imposing ventilation-driven CO2 outgassing in a carbonate weathering model, we show here that carbonate geochemistry is accelerated and does play a surprisingly large role in the observed CO2 exchange pattern of a semi-arid ecosystem. We found that by rapidly depleting soil CO2 during the daytime, ventilation disturbs soil carbonate equilibria and therefore strongly magnifies daytime carbonate precipitation and associated CO2 production. At night, ventilation ceases and the depleted CO2 concentrations increase steadily. Dissolution of carbonate is now enhanced, which consumes CO2 and largely compensates for the enhanced daytime carbonate precipitation. This is why only a relatively small effect on global carbonate weathering rates is to be expected. On the short term, however, ventilation has a drastic effect on synoptic carbonate weathering rates, resulting in a pronounced diel pattern that exacerbates the non-biological behavior of soil–atmosphere CO2 exchanges in dry regions \mbox{with carbonate soils}.M. Roland was granted by the Institute for Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen). I. A. Janssens and R. Van Grieken acknowledge the Research Foundation – Flanders (FWO). P. Serrano-Ortiz is funded by a postdoctoral fellowship from the Spanish Ministry of Science and Innovation. S. Cuezva was funded by a postdoctoral fellowship from the Spanish Ministry of Science and Innovation, research programme Juan de la Cierva