An amino acid mixture, enriched with Krebs cycle intermediates, enhances extracellular matrix gene expression in cultured human fibroblasts

: In the human body, the skin is one of the organs most affected by the aging process. Nutritional approaches aimed to counteract the age-induced decline of extracellular matrix (ECM) deposition could be a valuable tool to decrease the degenerative processes underlying skin aging. Here, we investigated the ability of a six-amino acid plus hyaluronic acid (6AAH) formulation enriched with tricarboxylic acid (TCA) intermediates to stimulate ECM gene expression. To this aim, human BJ fibroblasts were treated with 6AAH alone or plus succinate or malate alone or succinate plus malate (6AAHSM), and mRNA levels of several ECM markers were evaluated. 6AAHSM increased the expression of all the ECM markers significantly above 6AAH alone or plus only succinate or malate. Furthermore, in an in vitro oxidative damage model, 6AAHSM blunted the hydrogen peroxide-induced decline in ECM gene expression. Our data suggest that feeding cells with 6AAH enriched with TCAs could efficiently be employed as a non-pharmacological approach for counteracting skin aging

Effect of Chemically Induced Hypoxia on Osteogenic and Angiogenic Differentiation of Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells in Direct Coculture

Bone is an active tissue where bone mineralization and resorption occur simultaneously. In the case of fracture, there are numerous factors required to facilitate bone healing including precursor cells and blood vessels. To evaluate the interaction between bone marrow-derived mesenchymal stem cells (BMSC)-the precursor cells able to differentiate into bone-forming cells and human umbilical vein endothelial cells (HUVEC)-a cell source widely used for the study of blood vessels. We performed direct coculture of BMSC and HUVEC in normoxia and chemically induced hypoxia using Cobalt(II) chloride and Dimethyloxaloylglycine and in the condition where oxygen level was maintained at 1% as well. Cell proliferation was analyzed by crystal violet staining. Osteogenesis was examined by Alizarin Red and Collagen type I staining. Expression of angiogenic factor-vascular endothelial growth factor (VEGF) and endothelial marker-von Willebrand factor (VWF) were demonstrated by immunohistochemistry and enzyme-linked immunosorbent assay. The quantitative polymerase chain reaction was also used to evaluate gene expression. The results showed that coculture in normoxia could retain both osteogenic differentiation and endothelial markers while hypoxic condition limits cell proliferation and osteogenesis but favors the angiogenic function even after 1 of day treatment

Studying pyrolysis products of bottom-of-the-barrel fuel with Py-GCxGC- TOF/CSD/FID

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O Sistema Nacional de Pesquisa Agropecuária: proposta de implentação para um novo modelo de gestão e governança.

A agropecuária há muitos anos vem desempenhando um papel de grande relevância para o crescimento econômico brasileiro, possibilitando ao país ser um dos maiores exportadores mundiais de produtos agrícolas. Uma importante estrutura que contribui para este resultado positivo é o Sistema Nacional de Pesquisa Agropecuária (SNPA), que atualmente se encontra fragilizado devido à falta de coordenação e cooperação entre os atores, além da redução de recursos. Neste contexto, o Centro de Gestão e Estudos Estratégicos (CGEE), propôs uma alternativa de arranjo para a pesquisa agropecuária, que compreende a estruturação, no médio e longo prazo, de uma plataforma, que possibilitará a articulação, alinhamento e sinergia entre os atores envolvidos no processo de pesquisa e inovação para a agricultura do País. Este trabalho objetiva apresentar uma proposta de implementação, no curto prazo, para se alcançar o modelo formulado pelo CGEE. Realizamos um estudo de caso sobre o SNPA, por meio de uma breve revisão bibliográfica de conceitos pertinentes às necessidades de análise do Sistema. Descrevemos os principais eventos da trajetória do SNPA ocorridos entre 1972 e 2015 para entender seu funcionamento e sua dinâmica. A análise do Sistema foi realizada por meio do estudo de artigos, livros e teses sobre o caso e, em especial, por meio das entrevistas efetuadas com diferentes atores que representam o Sistema: acadêmicos, dirigentes e colaboradores das Organizações Estaduais de Pesquisa Agropecuária (OEPAs), dirigentes dos conselhos de representação, gestores públicos e representantes do setor privado. Constatamos que a implementação do modelo, para ser factível no curto prazo, deveria ser realizada por uma instituição que ocupasse papel preponderante no SNPA e que já dispusesse de mecanismos legais e de capacidade técnico-operacional necessários à validação e à execução do novo modelo. Foi possível identificar também a necessidade de inovações institucionais e organizacionais do Sistema, principalmente para atender às demandas dos produtores e da sociedade. Por fim, uma das mais relevantes constatações é a de que: a efetividade do novo arranjo só ocorrerá se as instituições e atores envolvidos se reconhecerem como coautores, tiverem proatividade e perceberem seu papel e suas responsabilidades.Orientada por Ana Cristina Braga Martes, FGV

Histological Evaluation and Management of Rare Case of Supernumerary "Ghost" Teeth

Supernumerary teeth are teeth that exceed the normal dental formula. Their prevalence in the permanent dentition is 1-14% and they occur more frequently in maxilla with a sex ratio of 2: 1 in favor of males. They are often associated with syndromes but there are examples of nonsyndromic multiple supernumerary teeth reported in the literature. CBCT is usually the best exam for radiographic diagnosis and treatment planning, because it provides 3D information about location and morphology of supernumerary teeth. This paper reports a rare case of four supernumerary teeth in a nonsyndromic 9-year-old boy. The peculiarity of this case is that two more exceeding teeth were found during surgical procedure. After extraction, all the teeth underwent a histological undecalcified processing for light microscopical examination. The two "ghost" supernumerary teeth seemed to be primordial dental germs, possibly resulting from an altered odontogenic process. After supernumerary teeth extraction, X-rays and exfoliation monitoring are recommended, since permanent retained teeth often erupt naturally or, at least, improve their condition. Radiographic follow-up is also useful in order to assess the formation of further teeth due to the hyperactivity of the dental lamina

Morphological and molecular characterization of human gingival tissue overlying multiple oral exostoses

Gingival and osseous augmentations are reported as hypertrophic or hyperplastic reactions to different factors including chronic traumatisms and surgeries such as free gingival graft (FGG) that induce an abnormal growth of both hard and soft tissues in genetically predisposed subjects. Since an imbalance in collagen turnover plays a key role in the development of gingival overgrowth leading to an accumulation of collagen in gingival connective tissue, in this study we described the histological and molecular features of three oral overgrowths obtained from a 34-year-old woman previously operated for FGG in order to evaluate a possible relationship between exostoses and overgrown tissue. Healthy and overgrown gingiva were analyzed by histological methods, and the expression of genes and proteins involved in collagen synthesis, maturation, and degradation was assessed in cultured fibroblasts obtained from gingival fragments at the molecular level. Our results show that general morphology and collagen content were similar in healthy and overgrown gingivae. However, fibroblasts obtained from the overgrown gingiva revealed an anabolic phenotype characterized by an increased collagen turnover and maturation. These findings indicate that an exostosis could act as a mechanical stimulus stretching the overlying connective tissue and triggering an anabolic phenotype of gingival fibroblasts and suggest to use minimally invasive surgical techniques to avoid traumatizing the periosteal tissues for the eradication of the exostosis with minimal relapses

Management of inherited von Willebrand disease in Italy : results from the retrospective study on 1234 patients

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is due to quantitative and/or qualitative defects of von Willebrand factor (VWF). Despite the improved knowledge of the disease, detailed data on VWD types requiring specific treatments have not been reported thus far. To determine the number and types of VWD requiring therapy with desmopressin (DDAVP) and/or VWF/FVIII concentrates in Italy, a national registry on VWD (RENAWI) was organized. Only 16 of 48 centers included VWD in the RENAWI with diagnoses performed locally. Patients with uncertain results were retested by two expert laboratories using multimeric analysis and mutations of the VWF gene. A total of 1234 of 1529 (81%) cases satisfied the inclusion criteria and could be classified as VWD1 (63%), VWD2A (7%), VWD2B (6%), VWD2M (18%), VWD2N (1%), and VWD3 (5%). VWD types were also confirmed by DNA analyses and occur in young adults (83%), mainly in women (58%). Mucosal bleedings (32 to 57%) are more frequent than hematomas (13%) or hemarthrosis (6%). Most patients were exposed to an infusion trial with desmopressin (DDAVP) and found responsive with the following rates: VWD1 (69%), VWD2A (26%), VWD2M (29%), and VWD2N (71%). However, DDAVP was not always used to manage bleeding in all responsive patients and VWF/FVIII concentrates were given instead of or together with DDAVP in VWD1 (30%), VWD2A (84%), VWD2B (62%), VWD2M (63%), VWD2N (30%), and VWD3 (91%). Data of the RENAWI showed that correct VWD identification and classification might be difficult in many Italian centers. Therefore, evidence-based studies should be organized only in well-characterized patients tested by laboratories that are expert in the clinical, laboratory, and molecular markers of VWD

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012