Vaginal sheets with Thymbra capitata essential oil for the treatment of bacterial vaginosis: design, characterization and in vitro evaluation of efficacy and safety

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with unpleasant odour. Excipients were selected to promote the healthy vaginal environment reestablishment and bioadhesion of formulations, while the TCEO acts directly on BV pathogens. We characterized vaginal sheets with TCEO in regard to technological characterization, predictable in vivo performance, in vitro efficacy and safety. Vaginal sheet D.O (acid lactic buffer, gelatine, glycerine, chitosan coated with TCEO 1% w/w) presented a higher buffer capacity and ability to absorb vaginal fluid simulant (VFS) among all vaginal sheets with EO, showing one of the most promising bioadhesive profiles, an excellent flexibility and structure that allow it to be easily rolled for application. Vaginal sheet D.O with 0.32 µL/mL TCEO was able to significantly reduce the bacterial load of all in vitro tested Gardnerella species. Although vaginal sheet D.O presented toxicity at some concentrations, this product was developed for a short time period of treatment, so this toxicity can probably be limited or even reversed when the treatment ends.This work supported by the Portuguese Foundation for Science and Technology within the research project PTDC/BIA-MIC/28271/2017 under the scope of COMPETE 2020 (POCI-01- 0145-FEDER-028271) including an individual scholarship and general funding. This work was also developed within the scope of the CICS-UBI projects UIDB/00709/2020 and UIDP/00709/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES.info:eu-repo/semantics/publishedVersio

Differences in chemical composition and antioxidant activity of three propolis samples collected in the same apiary

Financial support provided by FCT (PD/BD/128276/2017), under the Doctoral Programme Agrichains - PD/00122/2012

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD.Fundação para a Ciência e a Tecnologia-UID/Multi/0612/2019Unión Europea-D3i4AD), FP7-PEOPLE-2013-IAPP, GA 61234

Longitudinal study of patients with chronic Chagas cardiomyopathy in Brazil (SaMi-Trop project): a cohort profile.

PurposeWe have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants.ParticipantsThe study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50-74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample.Findings to dateClinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare.Future plansWe will continue following this patients' cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities.Trial registration numberNCT02646943; Pre-results

Robustness Diagram: a bridge between business modelling and system design

Use case driven development has proven being a good approach for capturing problem semantics in an orderly, structured description. However, it specifies an abstraction beyond practicity to guide system design process. Robustness diagrams are a simple solution for drafting a more formal description for business modelling. This very simplicity may, however, detract its value, falling short of capturing the rich business semantics. Stereotyping is the essence behind its robustness diagram mechanics. Symbols convey the abstraction necessary to catch the model semantics. Increasing the number of stereotypes we can achieve a closer match from model to design. Rules carefully stated for robustness diagram can help to translate highleveI information into well-behaved and predictable symbolic descriptions. This enhancement to robustness diagram helps to patch the gap between abstract model and project into a paved continuum. It has been used to train programmers to extract working and consistent systems out of use case specifications

Histologic and Histomorphometric Analysis of Posterior Region of the Human Temporomandibular Disc

Objective The aim of this study was to analyze histologic and histomorphometric features of the articular disc in groups with and without disc displacement. Study design A sample of 39 temporomandibular joints TMJs (31 case specimens, 8 control specimens) from 28 patients (mean age 31.2 years) were recruited for this study. The patients were considered to be affected and treated surgically with disc repositioning when presenting painful clinical signs of disc displacement after unsuccessful nonsurgical treatment for at least 6 months. Of the control patients, 4 presented condyle fracture which required opening to be reduced for treatment, and 4 displayed active condyle hyperplasia. The posterior region of the disc was removed and sent for histologic and histomorphometric analysis. Histologic (hematoxylin-eosin) and histomorphometric (picro-Sirius red) analyses were performed. Statistically significant differences between the analyzed groups were accessed through the chi-squared test (P ≤ .05). The Mann-Whitney U test was used to observe the differences between mean values when variables did not present normal distribution [Kolmogorov-Smirnov(a) test]. Results There were no significant differences between the groups in relation to the parameters studied by histologic and histomorphometric analysis (using or not using polarization). Conclusions To the limits of this study, there were no significant histologic and histomorphometric differences in the articular disc between groups with and without TMJ dysfunction

Field activities within an environmental sciences program: a b-learning case study

A reflection on the use of fieldwork in environmental science programmes is conducted in this paper. It is generally agreed that for fieldwork to be effective, it must serve a clear purpose in the curriculum. For a good curriculum design, a fieldwork course must complement, enhance or extend an existing part of the curriculum or fulfil some major objective of the curriculum as a whole. Thus a successful integration of fieldwork within an undergraduate degree programme is particularly important. For an environmental science course delivered through online methodology, it becomes evident that special attention should be devoted to the design and implementation of such a course. If we consider the more general definition where the field is seen as the location, outside the classroom setting, where learning takes place, then fieldwork is the set of activities that will facilitate students’ learning. It is generally agreed that a field course is much more difficult to integrate than a set of activities closely related to a specific subject. However, in a distance-learning university it is not plausible that students perform this type of activity very often. Therefore, the field courses are designed as a stand-alone module. The current work analyzes the design of the course entitled Fieldwork II which is integrated in the undergraduate degree in Environmental Sciences at Universidade Aberta. Many issues have to be taken into account when designing such a course that encompasses legislative, pedagogical and logistical matters. An overview of the research work that has been developed on the pedagogical value of fieldwork is given. Taking into account the specific learning methodology adopted at Universidade Aberta, we also present a fieldwork model for environmental sciences in a context of a blended learning (b-learning) undergraduate programme. The organizational effectiveness of the model and students’ participation was assessed in two scholar years of a fieldwork course at Universidade Aberta. Also, the project assignment synopses were assessed in the context of education for sustainability. Finally, it should be stressed that fieldwork should be regarded as a form of learning which exploits the unique characteristics of the field environment to improve the student learning experience.info:eu-repo/semantics/publishedVersio

Immunization against Pertussis: An Almost Solved Problem or a Headache in Public Health

Whooping cough or pertussis is a serious infectious disease of the human respiratory tract, caused by Gram-negative bacteria Bordetella pertussis and Bordetella parapertussisHU. The current pertussis vaccines may consist of dead cells of B. pertussis (whole cell pertussis vaccines—wPs) or purified antigens from the bacterium (acellular pertussis vaccines—aPs). The aPs are less reactogenic and have been widely used in developed countries for more than two decades, but their high cost of production makes them prohibitive for developing countries, and the accelerated rate of epidemic outbreaks has led to the hypothesis that aPs are less effective than the wP ones. Considering cost-effectiveness, some authors have pointed out questions about the possibility of reintroduction of wP vaccines into the primary doses of pertussis vaccination. The Butantan Institute in São Paulo, Brazil, developed a wP vaccine with low endotoxicity (Plow) obtained by chemical extraction of the lipooligosaccharide (LOS) fraction from the outer membrane of the bacterial cell, showing to be less reactogenic and equally immunogenic and protective as the traditional wP vaccine. The Plow may possibly be introduced into the vaccination schedule for immunization of adolescents and young adults in Brazil, an important epidemiological contribution to reducing the circulation of B. pertussis