Altered bone microarchitecture in a type 1 diabetes mouse model Ins2 Akita

Type 1 diabetes mellitus (T1DM) has been associated to several cartilage and bone alterations including growth retardation, increased fracture risk, and bone loss. To determine the effect of long term diabetes on bone we used adult and aging Ins2(Akita) mice that developed T1DM around 3-4 weeks after birth. Both Ins2(Akita) and wild-type (WT) mice were analyzed at 4, 6, and 12 months to assess bone parameters such as femur length, growth plate thickness and number of mature and preapoptotic chondrocytes. In addition, bone microarchitecture of the cortical and trabecular regions was measured by microcomputed tomography and gene expression of Adamst-5, Col2, Igf1, Runx2, Acp5, and Oc was quantified by quantitative real-time polymerase chain reaction. Ins2(Akita) mice showed a decreased longitudinal growth of the femur that was related to decreased growth plate thickness, lower number of chondrocytes and to a higher number of preapoptotic cells. These changes were associated with higher expression of Adamst-5, suggesting higher cartilage degradation, and with low expression levels of Igf1 and Col2 that reflect the decreased growth ability of diabetic mice. Ins2(Akita) bone morphology was characterized by low cortical bone area (Ct.Ar) but higher trabecular bone volume (BV/TV) and expression analysis showed a downregulation of bone markers Acp5, Oc, and Runx2. Serum levels of insulin and leptin were found to be reduced at all-time points Ins2(Akita). We suggest that Ins2(Akita) mice bone phenotype is caused by lower bone formation and even lower bone resorption due to insulin deficiency and to a possible relation with low leptin signaling.F. R. Carvalho and S. M. Calado acknowledge the financial support from the Portuguese Foundation for Science and Technology (FCT) through Ph.D. fellowships SFRH/BD/76429/2011 and SFRH/BD/76873/2011, respectively. This study was funded in part by CCMAR funding from European Regional Development Fund (ERDF) under COMPETE Program and through FCT under PEst-C/MAR/LA0015/2011 project and through UID/Multi/04326/2013 project. GA Silva was funded by (PIRG05-GA-2009-249314-EyeSee) and Research Center Grant UID/BIM/04773/2013 to CBMR

Marine collagen/apatite composite scaffolds envisaging hard tissue applications

The high prevalence of bone defects has become a worldwide problem. Despite the significant amount of research on the subject, the available therapeutic solutions lack efficiency.  Autografts, the most common used approaches to treat bone defects have limitations such as donor site morbidity, pain and lack of donor site. Marine resources emerge as an attractive alternative to extract bioactive compounds for further use in bone tissue engineering approaches. On one hand they can be isolated from by-products, at low costs, creating value from products that are considered waste for the fish transformation industry. One the other hand, religious constraints will be avoided. We isolated two marine origin materials, collagen from shark skin (Prionace glauca) and calcium phosphates from teeth of two different shark species (Prionace glauca and Isurus oxyrinchus), and further proposed to mix them to produce 3D composite structures for hard tissue applications. Two crosslinking agents, EDC/NHS and HMDI, were tested to enhance scaffoldsâ properties, with EDC/NHS resulting in better properties. The characterization of the structures showed that the developed composites could support attachment and proliferation of osteoblast-like cells. A promising scaffold for the engineering of bone tissue is thus proposed, based on a strategy of marine by-products valorisation.This work was funded by INTERREG under the POCTEP Project 0687_NOVOMAR_1_P and the Atlantic Area Transnational Cooperation Programme Project MARMED (2011-1/164), as well as by European Union FP7 under the project POLARIS (REGPOT-CT2012-316331).info:eu-repo/semantics/publishedVersio

Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents

© Cambridge University Press 2016We report the pharmacological activity of organoruthenium complexes containing chloroquine (CQ) as a chelating ligand. The complexes displayed intraerythrocytic activity against CQ-sensitive 3D7 and CQ-resistant W2 strains of Plasmodium falciparum, with potency and selectivity indexes similar to those of CQ. Complexes displayed activity against all intraerythrocytic stages, but moderate activity against Plasmodium berghei liver stages. However, unlike CQ, organoruthenium complexes impaired gametocyte viability and exhibited fast parasiticidal activity against trophozoites for P. falciparum. This functional property results from the ability of complexes to quickly induce oxidative stress. The parasitaemia of P. berghei-infected mice was reduced by treatment with the complex. Our findings demonstrated that using chloroquine for the synthesis of organoruthenium complexes retains potency and selectivity while leading to an increase in the spectrum of action and parasite killing rate relative to CQ.This research was funded by FAPESB (grant PET0042/2013, Brazil) to M.B.P.S, FAPESP (grant 14/10516-7, Brazil) to A.A.B. and Fundação para a Ciência e Tecnologia (grant PTDC/SAU-MIC/117060/2010 Portugal) to M.P. A.A.B. and M.B.P.S. are recipients of senior fellowships by CNPq (Brazil)info:eu-repo/semantics/publishedVersio

Prospective Study of Loss of Health-Related Quality Adjusted Life Years in Children and their Families due to Uncomplicated and Hospitalised Varicella

Introduction and aims: Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. Methods: Children with varicella in the community and admitted to hospitals in Portugal were included over 18 months from January 2019. Children's and carers' HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. Results: Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0 days (95 % CI 1.9-2.2, n = 101) (mean 5.4 QALYs/1000 children (95 % CI 5.3-6.1) and 1.3 days/primary carer (95 % CI 1.2-1.6, n = 103) (mean 3.6 QALYs /1000 carers (95 % CI 3.4-4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8 days (95 % CI 9.4-10.6, n = 114) (mean 26.8 QALYs /1000 children (95 % CI 25.8-29.0) and 8.5 days/primary carer (95 % CI 7.4-9.6, n = 114) (mean 23.4 QALYs/1000 carers (95 % CI 20.3-26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95 % CI 43.9-97.6)]. Estimates for children's QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. Conclusions: The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.info:eu-repo/semantics/publishedVersio

Wild dogs at stake: deforestation threatens the only Amazon endemic canid, the short-eared dog (Atelocynus microtis)

The persistent high deforestation rate and fragmentation of the Amazon forests are the main threats to their biodiversity. To anticipate and mitigate these threats, it is important to understand and predict how species respond to the rapidly changing landscape. The short-eared dog Atelocynus microtis is the only Amazon-endemic canid and one of the most understudied wild dogs worldwide. We investigated short-eared dog habitat associations on two spatial scales. First, we used the largest record database ever compiled for short-eared dogs in combination with species distribution models to map species habitat suitability, estimate its distribution range and predict shifts in species distribution in response to predicted deforestation across the entire Amazon (regional scale). Second, we used systematic camera trap surveys and occupancy models to investigate how forest cover and forest fragmentation affect the space use of this species in the Southern Brazilian Amazon (local scale). Species distribution models suggested that the short-eared dog potentially occurs over an extensive and continuous area, through most of the Amazon region south of the Amazon River. However, approximately 30% of the short-eared dog's current distribution is expected to be lost or suffer sharp declines in habitat suitability by 2027 (within three generations) due to forest loss. This proportion might reach 40% of the species distribution in unprotected areas and exceed 60% in some interfluves (i.e. portions of land separated by large rivers) of the Amazon basin. Our local-scale analysis indicated that the presence of forest positively affected short-eared dog space use, while the density of forest edges had a negative effect. Beyond shedding light on the ecology of the short-eared dog and refining its distribution range, our results stress that forest loss poses a serious threat to the conservation of the species in a short time frame. Hence, we propose a re-assessment of the short-eared dog's current IUCN Red List status (Near Threatened) based on findings presented here. Our study exemplifies how data can be integrated across sources and modelling procedures to improve our knowledge of relatively understudied species

The Parkinson disease pain classification system: Results from an international mechanism-based classification approach

Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 6 7.6 years) and 37 healthy controls were recruited in 4 centers. PDrelated pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain’s Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.Fil: Mylius, Veit. Universitat Phillips; Alemania. Center for Neurorehabilitation; Suiza. Kantonsspital St; SuizaFil: Perez Lloret, Santiago. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Cury, Rubens G.. Universidade de Sao Paulo; BrasilFil: Teixeira, Manoel J.. Universidade de Sao Paulo; BrasilFil: Barbosa, Victor R.. Universidade de Sao Paulo; BrasilFil: Barbosa, Egberto R.. Universidade de Sao Paulo; BrasilFil: Moreira, Larissa I.. Universidade de Sao Paulo; BrasilFil: Listik, Clarice. Universidade de Sao Paulo; BrasilFil: Fernandes, Ana M.. Universidade de Sao Paulo; BrasilFil: de Lacerda Veiga, Diogo. Universidade de Sao Paulo; BrasilFil: Barbour, Julio. Universidade de Sao Paulo; BrasilFil: Hollenstein, Nathalie. Universidade de Sao Paulo; BrasilFil: Oechsner, Matthias. Center for Neurological Rehabilitation; SuizaFil: Walch, Julia. Kantonsspital St; SuizaFil: Brugger, Florian. Kantonsspital St; SuizaFil: Hägele Link, Stefan. Kantonsspital St; SuizaFil: Beer, Serafin. Center for Neurorehabilitation; SuizaFil: Rizos, Alexandra. King's College Hospital; Reino UnidoFil: Chaudhuri, Kallol Ray. The Maurice Wohl Clinical Neuroscience Institute; Reino Unido. King's College Hospital; Reino UnidoFil: Bouhassira, Didier. Université Versailles-Saint-Quentin; Francia. Hôpital Ambroise Paré; FranciaFil: Lefaucheur, Jean Pascal. Université Paris-Est-Créteil; FranciaFil: Timmermann, Lars. Universitat Phillips; AlemaniaFil: Gonzenbach, Roman. Center for Neurorehabilitation; SuizaFil: Kägi, Georg. Kantonsspital St; SuizaFil: Möller, Jens Carsten. Universitat Phillips; Alemania. Center for Neurological Rehabilitation; SuizaFil: Ciampi de Andrade, Daniel. Universidade de Sao Paulo; Brasi

Biotransformation of Metal-Rich Effluents and Potential Recycle Applications

In this chapter, it was introduced about the metallurgic effluents, and their potential to be converted into some feasible coproducts for industries. Some possibilities to introduce circular economy in the context of metallurgic effluents, and in the same way, some techniques to promote bioremediation using microorganisms and products from them were also described. Reported studies, as well as some perspectives to use metal-rich effluents in agriculture and soil quality improvement, were also shown. Copper effluents were kept as the main candidate for sustainable use, as a potentially interesting material for circular economy approaches