O R I G I N A L P A P E R A Multiparadigmatic Model for a Holistic Nursing

Abstract Based on a primary stud

Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3ß survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.This work was funded by European Structural and Investment Funds (ESIF), under Lisbon Portugal Regional Operational Programme and National Funds through Fundação para a Ciência e Tecnologia (FCT) ([POCI-01-0145-FEDER-030985], [POCI-01-0145-FEDER-016385]); by FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of individual funding [CEECINST/00091/2018] to DN and by QREN funds through the project ClinUCX (QREN 30196) and individual fellowships: [PD/BD/127997/2016] to TL, [SFRH/BD/144490/2019] to RG and [SFRH/BD/111799/2015] to VS-P. The funding bodies other than ECBio had no role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication

Effects of the fibers distribution in the human eardrum: A biomechanical study

The eardrum separates the external ear from the middle ear and it is responsible to convert the acoustical energy into mechanical energy. It is divided by pars tensa and pars flaccida. The aim of this work is to analyze the susceptibility of the four quadrants of the pars tensa under negative pressure, to different lamina propria fibers distribution. The development of associated ear pathology, in particular the formation of retraction pockets, is also evaluated. To analyze these effects, a computational biomechanical model of the tympano-ossicular chain was constructed using computerized tomography images and based on the finite element method. Three fibers distributions in the eardrum middle layer were compared: case 1 (eardrum with a circular band of fibers surrounding all quadrants equally), case 2 (eardrum with a circular band of fibers that decreases in thickness in posterior quadrants), case 3 (eardrum without circular fibers in the posterior/superior quadrant). A static analysis was performed by applying approximately 3000Pa in the eardrum. The pars tensa of the eardrum was divided in four quadrants and the displacement of a central point of each quadrant analyzed. The largest displacements of the eardrum were obtained for the eardrum without circular fibers in the posterior/superior quadrant

Antinociceptive Activity of Thymoquinone and its Structural Analogues: A Structure-Activity Relationship Study

Purpose: To investigate the structural features that influence the antinociceptive activity of thymoquinone and their structural analogues.Methods: The quinones were prepared by an oxidation procedure using molecular oxygen and catalysis with [CoII(salen)] from the respective phenols. The antinociceptive activity of para-benzoquinones (10 mg/kg, ip) was evaluated using formalin test in mice. Vehicle (5 % Tween 80) or morphine (10 mg/kg) were used as control group and standard drug, respectively. The amount of time spent licking the injected paw was considered as the nociceptive response.Results: Among the compounds tested, five para-benzoquinones showed antinociceptive activity. The 2-isopropyl-para-benzoquinone presented the highest potency in first and second phases and produced a near-maximal inhibition (p < 0.001) in the formalin test, similar to morphine (p < 0.001).Conclusion: Our experimental results show that by appropriate structural modification of parabenzoquinones it may be possible to develop novel analgesic drugs.Keywords: Quinones, Antinociceptive activity, Analgesic, Central nervous system, Structure-activity relationship, Medicinal plant

Women living with HIV/AIDS who are sexual partners of injecting drug users

OBJECTIVE: To analyze perceptions of risk, prevention strategies, their own relationship with drug use and that of their partner's, and future expectations among women living with HIV/AIDS whose partners are drug users. METHODS: This is a qualitative study of women living with HIV/AIDS who receive specialist treatment in São Paulo Municipality. Semi-structured interviews were carried out with 15 women, whose self-reported means of infection were heterosexual relations with a partner who is an injecting drug user. The script for the interviews covered the following areas: childhood, history of sexual relations, use of drugs, impact of seropositivity on daily life, understanding of the prevention of sexually transmitted infections, and perspectives of the future. The material from the interviews was analyzed using content analysis. RESULTS: The study pointed to a difference in the ways that the women live with their own drug use and with that of their partners. Their partners' use of injecting drugs was not primarily associated with a risk of HIV infection, due to attempts to conceal the fact or because they believed that the monogamy-fidelity-confidence trinity would take precedence as a form of protection. CONCLUSIONS: The women's different experiences of drug use should be taken into account and opportunities to discuss with them about the issue are important to ensure that more effective strategies for prevention and care are adopted.OBJETIVO: Analisar as percepções de risco, as estratégias de prevenção, sua própria relação com o uso de drogas e do parceiro e suas expectativas quanto ao futuro relatadas por mulheres vivendo com HIV/Aids parceiras de usuários de drogas. MÉTODOS: Estudo qualitativo sobre mulheres vivendo com HIV/Aids, atendidas em serviço especializado no Município de São Paulo. Foram aplicadas entrevistas semi-estruturadas a 15 mulheres, cuja via de infecção auto-referida foram as relações heterossexuais com parceiro usuário de drogas injetáveis. O roteiro das entrevistas compreendia: infância, história dos relacionamentos amorosos, uso de drogas, impacto da soropositividade no cotidiano, compreensão sobre prevenção de infecções sexualmente transmissíveis, e visão do futuro. A interpretação das entrevistas foi realizada por meio de análise de conteúdo. RESULTADOS: O estudo indicou diversidade da convivência das mulheres com o uso de drogas próprio e do parceiro. O uso de drogas injetáveis pelo parceiro não foi, prioritariamente, associado ao risco de infecção por HIV/Aids, seja por estratégias de ocultamento do fato, seja por considerarem que a tríade monogamia-fidelidade-confiança teria primazia como forma de proteção. CONCLUSÕES: A diversidade da convivência das mulheres com o uso de drogas deve ser considerada e oportunidades de fala e escuta sobre a questão podem ser importantes para a adoção de estratégias mais efetivas de prevenção e cuidado.Universidade de São Paulo Faculdade de Medicina Departamento de Medicina PreventivaUniversidade Federal de São Paulo (UNIFESP) Departamento de Ciências da SaúdePrefeitura Municipal de São Paulo Secretaria Municipal de SaúdeUNIFESP, Depto. de Ciências da SaúdeSciEL

Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery

To develop and validate a clinical prediction model of patient-reported pain and function after undergoing total knee replacement (TKR). We used data of 1,649 patients from the Knee Arthroplasty Trial who received primary TKR across 34 centres in the UK. The external validation included 595 patients from Southampton University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors including patient characteristics and clinical factors were considered. Bootstrap backward linear regression analysis was used. Low pre-operative OKS, living in poor areas, high body mass index, and patient-reported anxiety or depression were associated with worse outcome. The clinical factors associated with worse outcome were worse pre-operative physical status, presence of other conditions affecting mobility and previous knee arthroscopy. Presence of fixed flexion deformity and an absent or damaged pre-operative anterior cruciate ligament (compared with intact) were associated with better outcome. Discrimination and calibration statistics were satisfactory. External validation predicted 21.1% of the variance of outcome. This is the first clinical prediction model for predicting self-reported pain and function 12 months after TKR to be externally validated. It will help to inform to patients regarding expectations of the outcome after knee replacement surgery

Carvacrol, (-)-borneol and citral reduce convulsant activity in rodents

Carvacrol, a monoterpenic phenol present in essential oils of the Labiatae family, has been used through the ages as a source of flavor in food and for medicinal purposes. Borneol is a monoterpene found in several species of Artemisia and Dipterocarpaceae, used for anxiety, pain and anesthesia in traditional Chinese. Citral, a mixture of two geometrical isomers (neral and geranial), is one of the most important compounds in some citrus oils and has central nervous system (CNS) properties. The anticonvulsant effect of carvacrol (CARV), (-)-borneol (BOR) and citral (CIT) was investigated in two animal models of epilepsy. Mice were pretreated with CARV, BOR or CIT (50, 100, and 200 mg/kg, i.p.) 30 min before pentylenetetrazole (PTZ) or maximal electroshock (MES) tests, the two most important animal epilepsy tests. The latency for development of convulsions and protection percentage was recorded. In order to investigate the involvement of GABAergic system, flumazenil was utilized. These monoterpenes, CARV in a higher, but not in a lower dose (p < 0.001), BOR and CIT in all doses (p < 0.05 or p < 0.001), were capable of promoting an increase of latency for the development of convulsions induced by PTZ. Additionally, these compounds were efficient in preventing the tonic convulsions (p < 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.Key words: Carvacrol, (-)-borneol, citral, anticonvulsant activit

Modeling the scaling properties of human mobility

While the fat tailed jump size and the waiting time distributions characterizing individual human trajectories strongly suggest the relevance of the continuous time random walk (CTRW) models of human mobility, no one seriously believes that human traces are truly random. Given the importance of human mobility, from epidemic modeling to traffic prediction and urban planning, we need quantitative models that can account for the statistical characteristics of individual human trajectories. Here we use empirical data on human mobility, captured by mobile phone traces, to show that the predictions of the CTRW models are in systematic conflict with the empirical results. We introduce two principles that govern human trajectories, allowing us to build a statistically self-consistent microscopic model for individual human mobility. The model not only accounts for the empirically observed scaling laws but also allows us to analytically predict most of the pertinent scaling exponents