139 research outputs found

    Assessing Vegetation Decline Due to Pollution from Solid Waste Management by a Multitemporal Remote Sensing Approach

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    Nowadays, the huge production of Municipal Solid Waste (MSW) is one of the most strongly felt environmental issues. Consequently, the European Union (EU) delivers laws and regulations for better waste management, identifying the essential requirements for waste disposal operations and the characteristics that make waste hazardous to human health and the envi-ronment. In Italy, environmental regulations define, among other things, the characteristics of sites to be classified as “potentially contaminated”. From this perspective, the Basilicata region is cur-rently one of the Italian regions with the highest number of potentially polluted sites in proportion to the number of inhabitants. This research aimed to identify the possible effects of potentially toxic element (PTE) pollution due to waste disposal activities in three “potentially contaminated” sites in southern Italy. The area was affected by a release of inorganic pollutants with values over the thresholds ruled by national/European legislation. Potential physiological efficiency variations of vegetation were analyzed through the multitemporal processing of satellite images. Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) images were used to calcu-late the trend in the Normalized Difference Vegetation Index (NDVI) over the years. The mul-titemporal trends were analyzed using the median of the non-parametric Theil–Sen estimator. Fi-nally, the Mann–Kendall test was applied to evaluate trend significance featuring areas according to the contamination effects on investigated vegetation. The applied procedure led to the exclu-sion of significant effects on vegetation due to PTEs. Thus, waste disposal activities during previ-ous years do not seem to have significantly affected vegetation around targeted sites

    Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase-B

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    A library of monosubstituted chalcones (1-17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases

    Similar levels of efficacy of two different maintenance doses of adalimumab on clinical severity and quality of life of patients with hidradenitis suppurativa

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    Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4-43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29-39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages

    Altered cofactor regulation with disease-associated p97/VCP mutations

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    Dominant mutations in p97/VCP (valosin-containing protein) cause a rare multisystem degenerative disease with varied phenotypes that include inclusion body myopathy, Paget’s disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. p97 disease mutants have altered N-domain conformations, elevated ATPase activity, and altered cofactor association. We have now discovered a previously unidentified disease-relevant functional property of p97 by identifying how the cofactors p37 and p47 regulate p97 ATPase activity. We define p37 as, to our knowledge, the first known p97-activating cofactor, which enhances the catalytic efficiency (k_(cat)/K_m) of p97 by 11-fold. Whereas both p37 and p47 decrease the K_m of ATP in p97, p37 increases the k_(cat) of p97. In contrast, regulation by p47 is biphasic, with decreased k_(cat) at low levels but increased k_(cat) at higher levels. By deleting a region of p47 that lacks homology to p37 (amino acids 69–92), we changed p47 from an inhibitory cofactor to an activating cofactor, similar to p37. Our data suggest that cofactors regulate p97 ATPase activity by binding to the N domain. Induced conformation changes affect ADP/ATP binding at the D1 domain, which in turn controls ATPase cycling. Most importantly, we found that the D2 domain of disease mutants failed to be activated by p37 or p47. Our results show that cofactors play a critical role in controlling p97 ATPase activity, and suggest that lack of cofactor-regulated communication may contribute to p97-associated disease pathogenesis

    Functional Myogenic Engraftment from Mouse iPS Cells

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    Direct reprogramming of adult fibroblasts to a pluripotent state has opened new possibilities for the generation of patient- and disease-specific stem cells. However the ability of induced pluripotent stem (iPS) cells to generate tissue that mediates functional repair has been demonstrated in very few animal models of disease to date. Here we present the proof of principle that iPS cells may be used effectively for the treatment of muscle disorders. We combine the generation of iPS cells with conditional expression of Pax7, a robust approach to derive myogenic progenitors. Transplantation of Pax7-induced iPS-derived myogenic progenitors into dystrophic mice results in extensive engraftment, which is accompanied by improved contractility of treated muscles. These findings demonstrate the myogenic regenerative potential of iPS cells and provide rationale for their future therapeutic application for muscular dystrophies

    Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape

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    We describe protein interaction quantitation (PIQ), a computational method for modeling the magnitude and shape of genome-wide DNase I hypersensitivity profiles to identify transcription factor (TF) binding sites. Through the use of machine-learning techniques, PIQ identified binding sites for >700 TFs from one DNase I hypersensitivity analysis followed by sequencing (DNase-seq) experiment with accuracy comparable to that of chromatin immunoprecipitation followed by sequencing (ChIP-seq). We applied PIQ to analyze DNase-seq data from mouse embryonic stem cells differentiating into prepancreatic and intestinal endoderm. We identified 120 and experimentally validated eight 'pioneer' TF families that dynamically open chromatin. Four pioneer TF families only opened chromatin in one direction from their motifs. Furthermore, we identified 'settler' TFs whose genomic binding is principally governed by proximity to open chromatin. Our results support a model of hierarchical TF binding in which directional and nondirectional pioneer activity shapes the chromatin landscape for population by settler TFs.National Institutes of Health (U.S.) (Common Fund 5UL1DE019581)National Institutes of Health (U.S.) (Common Fund RL1DE019021)National Institutes of Health (U.S.) (Common Fund 5TL1EB008540)National Institutes of Health (U.S.) (Grant 1U01HG007037)National Institutes of Health (U.S.) (Grant 5P01NS055923

    High levels of untreated distress and fatigue in cancer patients

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    The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration

    Prevalence of vertebral fractures in women and men in the population-based Tromsø Study

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    <p>Abstract</p> <p>Background</p> <p>Osteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway.</p> <p>Methods</p> <p>Data was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant.</p> <p>Results</p> <p>The prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (<it>p </it>= 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures.</p> <p>Conclusions</p> <p>The prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.</p

    La merienda escolar, aliada de la buena alimentaciĂłn

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    En Argentina menos de 30 productos representan más de la mitad del gasto en alimentos de los hogares pobres, y más del 85% de las calorías y nutrientes ingeridos. La alimentación en los sectores de menores ingresos es muy parecida en todo el territorio, si bien en el Noroeste un poco más de mandioca o en el Sur un poco más de cordero. La dieta de los pobres es monótona por problemas económicos y determina déficit de nutrientes y micronutrientes. En los hogares de nivel socioeconómico medio-alto aún conserva rasgos de monotonía por exceso en el consumo de alimentos muy industrializados, alto contenido de azúcares y grasas saturadas y pobre contenido de fibra. En la Provincia de San Luis, se ha reglamentado la LEY Nº III-0743-2010 “MEjor alimentacion, mas salud”, homologada por el Decreto del Poder Ejecutivo Nº  2826, por el cual se ha implementado también un Programa del Ministerio de Salud de la Provincia, con el objetivo de difundir en las escuelas el establecimiento de “Kioscos  saludables”, con el propósito fundamental de proveer a los distintos actores de la comunidad educativa una merienda que respete las características de saludable, accediendo a ella en forma responsable y voluntaria, respetando las Leyes de la Nutrición: suficiente, completa, armónica, adecuada e inocua. Desde el Programa de Extensión de la Universidad Nacional de San Luis, en colaboración con INTA San Luis, nos propusimos investigar la realidad en una escuela de nivel medio de la ciudad de Villa Mercedes (S.L) junto a docentes del nivel primario y secundario de la escuela. Se realizaron talleres para indagar los hábitos alimenticios de niños de 5to grado, (tres divisiones). Se usaron técnicas de juego y grupos donde los niños pudieron expresar mediante dibujos y recortes tres consignas: 1) qué les gustaba comer, 2) qué comían habitualmente, 3) qué alimentos no habían comido nunca. Se valoraron los alimentos más nutritivos y a su vez sanos y se brindaron recomendaciones para la buena alimentación a niños y mediante trípticos divulgativos llegamos a sus padres. Los resultados obtenidos luego de la evaluación de las encuestas y los afiches mostró que los niños de clase media tienen una dieta poco variada, que hay muchos alimentos que nunca se han probado y que sus gustos van dirigidos a alimentos de alto contenido graso y poco valor nutricional. Se espera en el segundo año de ejecución del proyecto indicadores de cambio de hábitos nutricionales en los alumnos con los que se ha trabajado en la concientización y educación en dieta saludable. 
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