Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier

The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8 fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5wt% of enzyme functionalized NPs to 5wt% intestinal mucin led to c.a. 2 fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a lengthscale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential then PAP functionalized NPs as mucus permeating drug delivery systems

As teorias de enfermagem de Roy e Orem Intrínsecas à sistematização da assistência de enfermagem para promoção da saúde / Roy's nursing theories and orem intrinsic to the systematization of nursing care for health promotion

As teorias de enfermagem atuam como suplementos para o desenvolvimento da Sistematização da Assistência de Enfermagem, é a partir delas que o enfermeiro se baseia cientificamente e estabelece planos de cuidados orientados e clinicamente científicos para a promoção da saúde. Esta revisão objetivou descrever os principais elementos das teorias do autocuidado e adaptação e suas associações para a prática clínica a partir da Sistematização da Assistência de Enfermagem. Trata-se de uma Revisão Narrativa da Literatura, de caráter descritivo e abordagem qualitativa, desenvolvida a partir da Biblioteca Virtual em Saúde e bases de dados LILACS, BDENF e MEDLINE. As teorias de enfermagem atuam como um grande amparo para o desenvolvimento do exercício do enfermeiro, uma vez que estas são fundamentos teóricos/científicos que delineiam planos adequados para implementação da assistência e efetividade do plano de cuidados rentabilizando benefícios para a saúde de usuários dos sistemas de saúde. Diante do contexto, a aplicação de tais teorias dentro da sistematização viabiliza o Processo de Enfermagem, de modo a contribuir com a assistência qualificada que aborda o paciente de forma holística, considerando os aspectos sociais, familiares e físicos

Livro Verde dos Montados

O Livro Verde dos Montados apresenta diversos objectivos que se interligam: Em primeiro lugar, o Livro Verde pretende reunir e sistematizar, de uma forma simples e acessível ao público, o conhecimento produzido em Portugal pelos investigadores e técnicos de várias instituições de investigação ou de gestão que estudam o Montado. Assume-se como uma oportunidade de caracterizar o sistema tendo em conta as suas várias dimensões, identificando as principais ameaças à sua preservação assim como os caminhos que podem ajudar à sua sustentabilidade. Não sendo um documento científico, baseia-se no conhecimento científico e pretende constituir a base para uma plataforma de organização, tanto dos investigadores como do conhecimento científico actualmente produzido em Portugal sobre o Montado.Em segundo lugar, o Livro Verde deverá contribuir para um entendimento partilhado do que é o Montado, por parte do público, de técnicos e de especialistas, conduzindo a uma classificação mais clara do que pode ser considerado Montado e de quais os tipos distintos de Montados que podem ser identificados. Em terceiro lugar, o Livro Verde estabelece as bases para uma estratégia coordenada de disponibilização de informação sobre o sistema Montado, visando o seu conhecimento, apreciação e valorização pela sociedade portuguesa no seu conjunto. Deste modo, o Livro Verde poderá constituir um instrumento congregador e inspirador para a realização de acções de sensibilização e informação sobre o Montado. Em quarto lugar, pretende-se que o Livro Verde contribua para um maior reconhecimento e valorização do Montado como sistema, a nível do desenho das políticas nacionais por parte dos vários sectores envolvidos.Finalmente, o Livro Verde constituirá um documento parceiro do Livro Verde das Dehesas, produzido em Espanha em 2010, de forma a reforçar o reconhecimento e a devida valorização destes sistemas silvo-pastoris no desenho das estratégias e políticas relevantes pelas instituições europeias. Em suma, os autores pretendem que o Livro Verde dos Montados se afirme como o primeiro passo para uma efectiva definição e implementação de uma estratégia nacional para os Montados

Methods to determine the interactions of micro- and nanoparticles with mucus

The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. To have a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field

A Narrative Review of Motor Competence in Children and Adolescents: What We Know and What We Need to Find Out

Lack of physical activity is a global public health problem causing not only morbidity and premature mortality, but it is also a major economic burden worldwide. One of the cornerstones of a physically active lifestyle is Motor Competence (MC). MC is a complex biocultural attribute and therefore, its study requires a multi-sectoral, multi-, inter- and transdisciplinary approach. MC is a growing area of research, especially in children and adolescents due to its positive association with a plethora of health and developmental outcomes. Many questions, however, remain to be answered in this field of research, with regard to: (i) Health and Developmental-related Associations of MC; (ii) Assessment of MC; (iii) Prevalence and Trends of MC; (iv) Correlates and Determinants of MC; (v) MC Interventions, and (vi) Translating MC Research into Practice and Policy. This paper presents a narrative review of the literature, summarizing current knowledge, identifying key research gaps and presenting questions for future investigation on MC in children and adolescents. This is a collaborative effort from the International Motor Competence Network (IMCNetwork) a network of academics and researchers aiming to promote international collaborative research and knowledge translation in the expansive field of MC. The knowledge and deliverables generated by addressing and answering the aforementioned research questions on MC presented in this review have the potential to shape the ways in which researchers and practitioners promote MC and physical activity in children and adolescents across the worl

Alfabetização baseada na ciência: manual do curso ABC

O presente manual faz parte do projeto ABC – Alfabetização Baseada na Ciência, fruto de um Acordo de Cooperação Internacional celebrado entre a Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), a Faculdade de Psicologia e de Ciências da Educação da Universidade do Porto (FPCEUP), o Instituto Politécnico do Porto (IPP) e a Universidade Aberta de Portugal (UAb). Essa importante parceria tem o objetivo de contribuir para a formação continuada dos profissionais da educação brasileiros que atuam na área de alfabetização, somando-se aos vários esforços que têm sido envidados pelo Ministério da Educação (MEC) para elevar a qualidade dos processos de alfabetização no Brasil e, consequentemente, os seus resultados. A formação de professores tem sido um dos pilares da Política Nacional de Alfabetização (PNA), instituída pelo MEC por meio do Decreto 9.765/19, a qual destaca entre seus princípios a fundamentação de programas e ações em evidências provenientes das ciências cognitivas, bem como a adoção de referenciais de políticas públicas exitosas, nacionais e estrangeiras, baseadas em evidências científicas.info:eu-repo/semantics/publishedVersio

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients