Dynamics of the Desai-Zwanzig model in multiwell and random energy landscapes

We analyze a variant of the Desai-Zwanzig model [J. Stat. Phys. {\bf 19}1-24 (1978)]. In particular, we study stationary states of the mean field limit for a system of weakly interacting diffusions moving in a multi-well potential energy landscape, coupled via a Curie-Weiss type (quadratic) interaction potential. The location and depth of the local minima of the potential are either deterministic or random. We characterize the structure and nature of bifurcations and phase transitions for this system, by means of extensive numerical simulations and of analytical calculations for an explicitly solvable model. Our numerical experiments are based on Monte Carlo simulations, the numerical solution of the time-dependent nonlinear Fokker-Planck (McKean-Vlasov equation), the minimization of the free energy functional and a continuation algorithm for the stationary solutions

Cartilage tissue engineering using electrospun PCL nanofiber meshes and MSCs

Mesenchymal stem cells (MSCs) have been recognized for their ability to differentiate into cells of different tissues such as bone, cartilage, or adipose tissue, and therefore are of great interest for potential therapeutic strategies. Adherent, colony-forming, fibroblastic cells were isolated from human bone marrow aspirates, from patients undergoing knee arthroplasties, and the MSCs phenotype characterized by flow cytometry. Afterward, cells were seeded onto electrospun polycaprolactone nanofiber meshes and cultured in a multichamber flow perfusion bioreactor to determine their ability to produce cartilagineous extracellular matrix. Results indicate that the flow perfusion bioreactor increased the chondrogenic differentiation of hBM-MSCs, as confirmed either by morphological and RT-PCR analysis. Cartilage-related genes such as aggrecan, collagen type II, and Sox9 were expressed. ECM deposition was also detected by histological procedures. Collagen type II was present in the samples, as well as collagen type I. Despite no statistically significant values being obtained for gene expression, the other results support the choice of the bioreactor for this type of culture.M. Alves da Silva would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for her grant (SFRH/BD/28708/2006). The authors would like to acknowledge the patients of Hospital de S. Marcos, Braga, Portugal, for the donation of the biological samples, as well to its medical staff. The authors would also like to thank the Institute for Health and Life Sciences (ICVS), University of Minho, Braga, Portugal, for allowing the use of their research facilities. Authors would like specially to acknowledge Luis Martins for his valuable help with the histological procedures and Goreti Pinto for the aid in the microscopy. We thank Ana M. Frias for the important help with the FACS procedure. Finally, we would like to acknowledge the European NoE EXPERTISSUES (NMP3-CT-2004-500283). This work was partially supported by the European FP7 Project Find and Bind (NMP4-SL-2009-229292)

In vivo biodistribution of carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles in rats

Carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (CMCht/PAMAM) have recently been proposed for intracellular drug delivery purposes. These are constituted by a PAMAM dendrimer core grafted with chains of CMCht. Previous reports have shown that these nanoparticles disclosed an improved cytotoxic profile when compared to traditional dendrimers. Following on these results the present study aims to assess, for the first time, the short-term in vivo biodistribution of CMCht/PAMAM dendrimer nanoparticles upon intravenous injections in Wistar Han rats. The rats were injected in the tail vein with 1 and 10 µg/g, respectively, of fluorescein isothiocyanate (FITC) labeled CMCht/PAMAM dendrimer nanoparticles. Brain, liver, kidney and lung were collected at 24, 48 and 72 hours after injection and further stained with phalloidin-TRITC (red) and DAPI (blue) to trace the nanoparticles within the tissues. Liver, kidney and lung were also stained for haematoxylin and eosin in order to assess possible alterations in the morphology of these organs. CMCht/PAMAM dendrimer nanoparticles were observed within the vascular space and parenchyma of liver, kidney and lung, and in the choroid plexus, after 24, 48 and 72 hours upon intravenous injection of nanoparticles. No particles were observed in the brain parenchyma, nor any apparent deleterious histological changes, were observed within these organs. The present report revealed that CMCht/PAMAM dendrimer nanoparticles were stable in circulation for periods up to 72 hours, targeting the main organs/systems through internalization by the cells present in their parenchyma. These results provide positive indicators to their potential use in the future as intracellular drug delivery systems.Funds attributed by Fundação Calouste de Gulbenkian to A.J. Salgado under the scope of the The Gulbenkian Programme to Support Research in Life Sciences; Portuguese Foundation for Science and Technology (Science 2007 Program – A.J. Salgado, pre- and postdoctoral fellowships to J.M. Oliveira – SFRH/BPD/63175/2009, A.M. Frias – SFRH/BPD/45206/2008, F. Marques – SFRH/BPD/33379/2008, A.M. Falcão – SFRH/BD/44485/2008, S. Roque – SFRH/BD/24539/2005; S.R. Cerqueira – SFRH/BD/SFRH/BD/48406: 2008)

Overcoming challenges in pediatric formulation with a patient-centric design approach: a proof-of-concept study on the design of an oral solution of a bitter drug

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in‐use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in‐use stability protocols should be preferred in the stability evaluation of pediatric formulations.This work was supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., Portugal, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. This research was also supported by and Federal Government of Nigeria NEEDS Assessment grant‐2018. The authors are grateful to FCT (Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and to the Associate Laboratory SusTEC (LA/P/0007/2020). Ítala M.G. Marx also acknowledges the Ph.D. research grant (SFRH/BD/137283/2018) provided by FCT.info:eu-repo/semantics/publishedVersio

Occupational stress in health professionals: a study with Portuguese Nurses

Este trabalho analisa o estresse ocupacional em 286 enfermeiros de hospitais e centros de saúde portugueses. Avaliaram-se as fontes de estresse, o burnout, os problemas de saúde física, a satisfação e a realização profissional. Os resultados apontaram 30% de enfermeiros com experiências significativas de estresse e 15% com problemas de exaustão emocional. As análises de regressão múltipla apontaram maior capacidade preditiva das dimensões de estresse na exaustão emocional, na saúde física, na satisfação e na realização profissional. As análises comparativas evidenciaram maiores problemas de stresse e reacções mais negativas ao trabalho nas mulheres, nos enfermeiros mais novos e com menor experiência, nos trabalhadores com contratos a prazo, nos profissionais que realizam trabalho por turnos e nos que trabalham mais horas.This work analyses occupational stress in 286 nurses from hospitals and health care centres in Portugal. The following dimensions were evaluated: stress, burnout, physical health problems, satisfaction and professional fulfilment. Results revealed significant stress experiences in 30% of the professionals, and emotional exhaustion problems in 15%. Multiple regression analysis pointed out stress as an important predictor of emotional exhaustion, physical health, satisfaction and professional fulfilment. Comparative analysis suggested more occupational stress and professional negative experiences in the following groups: female nurses, younger and less experienced nurses, those with short-term working contracts, nurses working on a shift-basis system, and nurses working during long hours.(undefined

Stress and psychological health: testing the mediating role of cognitive appraisal

This study tested the mediating role of primary (e.g., threat and challenge perceptions) and secondary (e.g., coping potential and control perception) cognitive appraisal in the relationship between occupational stress and psychological health. This mediation was tested using a cross-sectional study based on self-reported measures. The total sample consisted of 2,302 nurses, 1,895 females (82.3%) and 407 males (17.7%), who completed an evaluation protocol with measures of occupational stress, cognitive appraisal, and psychological health. To test the mediating role of cognitive appraisal in the relationship between cognitive appraisal and psychological health, we used Structural Equation Modeling (SEM). The results confirmed that primary and secondary cognitive appraisals partially mediated the relationship between occupational stress and psychological health; however, the direct effects of stress on psychological health cannot be ignored. The findings indicated that cognitive appraisal is an important underlying mechanism in explaining adaptation at work.This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of MInho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)

Ferroelectric nanofibers with an embedded optically nonlinear benzothiazole derivative

We report measurements of the molecular first hyperpolarizability, thermal stability, photophysical, piezoelectric and ferroelectric properties of a benzothiazole derivative bearing an arylthiophene π-conjugated bridge both in solution and when embedded into a poly (L-lactic acid) (PLLA) matrix in the form of electrospun fibers with an average diameter of roughly 500 nm. The embedded nanocrystalline phenylthienyl-benzothiazole derivative, with crystal sizes of about 1.4 nm resulted in a good piezoelectric response from these functionalized electrospun fibers, indicative of a polar crystalline structure.Fundação para a Ciência e a Tecnologia (FCT

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe