Uncovering the neuroprotective mechanisms of curcumin on transthyretin amyloidosis

Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.This research was funded by the European Regional Development Fund (FEDER) through the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, grant number Norte-01-0145-FEDER-000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S. Nelson Ferreira was a recipient of a Postdoctoral Fellowship R171-2014-591 from Lundbeck foundation and by Lundbeck Foundation grant R248-2016-2518 for Danish Research Institute of Translational Neuroscience—DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Aarhus University, Denmark

How big does the effect of an intervention have to be? Application of two novel methods to determine the smallest worthwhile effect of a fall prevention programme: A study protocol

Introduction: This project concerns the identification of the smallest worthwhile effect (SWE) of exercise-based programmes to prevent falls in older people. The SWE is the smallest effect that justifies the costs, risks and inconveniences of an intervention and is used to inform the design and interpretation of systematic reviews and randomised clinical trials. Methods and analysis: This study will comprise two different methodological approaches: the benefitharm trade-off method and the discrete choice experiment to estimate the SWE of exercise interventions to prevent falls in older people. In the benefit-harm trade-off method, hypothetical scenarios with the benefits, costs, risks and inconveniences associated with the intervention will be presented to each participant. Then, assuming a treatment effect of certain magnitude, the participant will be asked if he or she would choose to have the intervention. The size of the hypothetical benefit will be varied up and down until it is possible to identify the SWE for which the participant would choose to have the intervention. In the discrete choice experiment, the same attributes (benefits, costs, risks and inconveniences) with varying levels will be presented as choice sets, and participants will be asked to choose between these choice sets. With this approach, we will determine the probability that a person will consider the effects of an intervention to be worthwhile, given the particular costs, risks and inconveniences. For each of the two approaches, participants will be interviewed in person and on different occasions. A subsample of the total cohort will participate in both interviews. Ethics and dissemination: This project has received Ethics Approval from the University of Sydney Human Ethics Committee (Protocol number: 14404). Findings will be disseminated through conference presentations, seminars and peer-reviewed scientific journals

a systematic review on sampling methods

PMCID: 4627393 PMID: 26518345BACKGROUND: In public health, hard-to-reach populations are often recruited by non-probabilistic sampling methods that produce biased results. In order to overcome this, several sampling methods have been improved and developed in the last years. The aim of this systematic review was to identify all current methods used to survey most-at-risk populations of men who have sex with men and sex workers. The review also aimed to assess if there were any relations between the study populations and the sampling methods used to recruit them. Lastly, we wanted to assess if the number of publications originated in middle and low human development (MLHD) countries had been increasing in the last years. METHODS: A systematic review was conducted using electronic databases and a total of 268 published studies were included in the analysis. RESULTS: In this review, 11 recruitment methods were identified. Semi-probabilistic methods were used most commonly to survey men who have sex with men, and the use of the Internet was the method that gathered more respondents. We found that female sex workers were more frequently recruited through non-probabilistic methods than men who have sex with men (odds = 2.2; p < 0.05; confidence interval (CI) [1.1-4.2]). In the last 6 years, the number of studies based in middle and low human development countries increased more than the number of studies based in very high and high human development countries (odds = 2.5; p < 0.05; CI [1.3-4.9]). CONCLUSIONS: This systematic literature review identified 11 methods used to sample men who have sex with men and female sex workers. There is an association between the type of sampling method and the population being studied. The number of studies based in middle and low human development countries has increased in the last 6 years of this study.publishersversionpublishe

Multiple gestation epidemiology--15 years survey

Between January of 1987 and December of 2001 were born 1243 twins related to 609 multiple pregnancies, in Maternidade Bissaya-Barreto. Data were grouped in periods of three years and several parameters were studied. The rate of multiple gestation has increased probably due to the contribution of the assisted conception techniques, and to the increase of the number of multiple fetal pregnancies (two or more) and to the increase of the mother age. These more frequent obstetric problems were preterm birth, gestational hypertension and abnormal sonographic data of fetal growth. The average age of delivery was 34 weeks and the birth weight has decreased. The most important factors for neonatal morbidity were hyaline membranous disease, intraventricular haemorrhage and the twin-twin transfusion syndrome. The neonatal mortality decreased in the last studied period

Immunomodulatory properties of Musa paradisiaca L. inflorescence in Combined Allergic Rhinitis and Asthma Syndrome (CARAS) model towards NFκB pathway inhibition

Musa paradisiaca L. (Musaceae), a tropical plant named banana is used as food and as medicine in Brazil. Banana inflorescence, popularly known as mangará, presents several biological activities including anti-inflammatory effects. Here, we demonstrated the immunomodulatory activity of banana inflorescence extract (HEM) on a mice model of combined allergic rhinitis and asthma syndrome (CARAS) and in human macrophages. The HEM inhibited the eosinophil migration, production of cytokines as IL-4, IL-5, IL-13, and IL-17A dependent on IFN-¿ production in the airway. The mechanism of the extract was, in part, by the NF-¿B signaling pathway inhibition. Besides, the HEM decreased expression of the CD86 and HLA-DR receptors on human M1 macrophages independently of M2 modulation. Therefore, we infer that the inflorescence, a disposable material from the banana crops, has anti-allergic property in the CARAS model and modulates the human macrophages, characterizing it as biologically important material for the production of phytomedicine.This work was supported by Brazilian agencies National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), Institute for Research and Innovation in Health (I3S) and National Institute of Biomedical Engineering (INEB). The authors would like to thank Serviço de Imunohemoterapia of Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal, for kindly donating Buffy Coats. The authors are also grateful for the valuable assistance provided by agencies, institutes and collaborators. This work was supported by Brazilian agencies National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), Institute for Research and Innovation in Health (I3S) and National Institute of Biomedical Engineering (INEB). The authors would like to thank Serviço de Imunohemoterapia of Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal, for kindly donating Buffy Coats. The authors are also grateful for the valuable assistance provided by agencies, institutes and collaborators

Brazilian Bidens pilosa Linne´ yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC50&sim;4.3-32.3 mg/ml) followed by the crude extract (IC50&sim;14.2-98.0 mg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6&plusmn;0.2 and 2.1&plusmn;0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3&prime;-dimethyl ether 7-&Omicron;-&beta;-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl4-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl4-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (&sim;60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases.Keywords: Bidens pilosa L.; hydroethanol maceration; ethyl acetate fractionation; free radical scavenger; hepatoprotection; CCl4 toxicit

Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk

Why are tapes better than wires in knotless rotator cuff repairs? An evaluation of force, pressure and contact area in a tendon bone unit mechanical model

Knotless repairs have demonstrated encouraging performance regarding retear rate reduction, but literature aiming at identifying the specific variables responsible for these results is scarce and conflictive. The purpose of this paper was to evaluate the effect of the material (tape or wire suture) and medial tendon passage (single or double passage) on the contact force, pressure and area at the tendon bone interface in order to identify the key factors responsible for this repairs´ success.info:eu-repo/semantics/publishedVersio