DISCOVERING THE EVERYDAY LANDSCAPE A cultural heritage education project in the urban periphery

Heritage and landscape education is crucial to training young people in active and responsible citizenship, protection of the public assets, appreciation of the cultural diversity and intergenerational dialogue. Therefore, it cannot be limited to sporadic experiences and on outstanding heritage and contexts but must be transdisciplinary, inclusive and practicable everywhere. This book relates the research and action project “Scuola Attiva Risorse” (ScAR), winner of the Polisocial Award that recognizes research for social purposes at the Politecnico di Milano. The text describes an experimental and innovative action delivered within the fragile context of the urban peripheries. This participatory process involved schools, universities, cultural institutions, administrations and private actors in interpreting and enhancing the “hidden” cultural heritage in Milan’s fringe neighbourhoods

Morphometric analysis of hepatocellular nodular lesions in HCV cirrhosis

Background and aims. We generated a computerized morphometric model to evaluate and quantify the morphological features in large regenerative nodules (LRN), high-grade dysplastic nodules (HGDN) and hepatocellular carcinoma (HCC). Methods. Sixteen LRN, 10 HGDN and 16 HCC in HCV-cirrhotic livers, were stained with H&E, smooth muscle actin, CD34, CD31 and reticulin to evaluate volume and surface fractions. Results. On H&E stains, the features most discriminatory between LRN, HGDN and HCC were volume fraction and number of hepatocytes nuclei in unit volume, and hepatocyte nuclear/cytoplasmic ratio. On immunohistochemistry, volume fractions of capillarised sinusoids, capillary units and isolated arteries were significantly different among all groups and highest in HCC; surface fraction of reticulin was markedly decreased in HCC. Conclusions. Our morphometric model is an objective method of quantification of the morphological changes of the nodular lesions and it could be applied in studies involving histological evaluation of the spectrum of nodular lesions arising in the cirrhotic liver

Assessing the effects of mining projects on child health in sub-Saharan Africa: a multi-country analysis

BACKGROUND: The African continent hosts many industrial mining projects, and many more are planned due to recent prospecting discoveries and increasing demand for various minerals to promote a low-carbon future. The extraction of natural resources in sub-Saharan Africa (SSA) represents an opportunity for economic development but also poses a threat to population health through rapid urbanisation and environmental degradation. Children could benefit from improved economic growth through various channels such as access to high-quality food, better sanitation, and clean water. However, mining can increase food insecurity and trigger local competition over safe drinking water. Child health can be threatened by exposure to mining-related air, noise, and water pollution. To assess the impact of mines on child health, we analyse socio-demographic, health, and mining data before and after several mining projects were commissioned in SSA. RESULTS: Data of 90,951 children living around 81 mining sites in 23 countries in SSA were analysed for child mortality indicators, and 79,962 children from 59 mining areas in 18 SSA countries were analysed for diarrhoea, cough, and anthropometric indicators. No effects of the launch of new mining projects on overall under-five mortality were found (adjusted Odds Ratio (aOR): 0.88; 95% Confidence Interval (CI): 0.68-1.14). However, activation of mining projects reduced the mortality risk among neonates (0-30 days) by 45% (aOR: 0.55; 95% CI: 0.37-0.83) and risk for a child to develop diarrhoeal diseases by 32% (aOR: 0.68; 95% CI: 0,51-0.90). The timing analysis of observed changes showed that there is a significant decline in the risk for childhood diarrhoea (aOR: 0.69; 95% CI: 0.49-0.97), and the mean height-for-age z-scores by 28 percentage points, during the prospection and construction phase; i.e., within four years to the initiation of extraction activity. No effects were found for cough and weight-for-height. CONCLUSION: The results presented suggest that the impacts of mining on child health vary throughout the mine's life cycle. Mining development likely contributes positively to the income and livelihoods of the impacted communities in the initial years of mining operations, particularly the prospection and construction phase; these potential benefits are likely to be at least partially offset by food insecurity and environmental pollution during early and later mining stages, respectively. Further research is warranted to better understand these health impacts and to identify policies that can help sustain the positive initial health impacts of mining projects in the long term

A roadmap for using DHIS2 data to track progress in key health indicators in the Global South: experience from sub-Saharan Africa

High quality health data as collected by health management information systems (HMIS) is an important building block of national health systems. District Health Information System 2 (DHIS2) software is an innovation in data management and monitoring for strengthening HMIS that has been widely implemented in low and middle-income countries in the last decade. However, analysts and decision-makers still face significant challenges in fully utilizing the capabilities of DHIS2 data to pursue national and international health agendas. We aimed to (i) identify the most relevant health indicators captured by DHIS2 for tracking progress towards the Sustainable Development goals in sub-Saharan African countries and (ii) present a clear roadmap for improving DHIS2 data quality and consistency, with a special focus on immediately actionable solutions. We identified that key indicators in child and maternal health (e.g. vaccine coverage, maternal deaths) are currently being tracked in the DHIS2 of most countries, while other indicators (e.g. HIV/AIDS) would benefit from streamlining the number of indicators collected and standardizing case definitions. Common data issues included unreliable denominators for calculation of incidence, differences in reporting among health facilities, and programmatic differences in data quality. We proposed solutions for many common data pitfalls at the analysis level, including standardized data cleaning pipelines, k-means clustering to identify high performing health facilities in terms of data quality, and imputation methods. While we focus on immediately actionable solutions for DHIS2 analysts, improvements at the point of data collection are the most rigorous. By investing in improving data quality and monitoring, countries can leverage the current global attention on health data to strengthen HMIS and progress towards national and international health priorities

Unusual skin toxicity associated with sustained disease response induced by nivolumab in a patient with non-small cell lung cancer

Introduction: Immunotherapy has shown efficacy in the treatment of different malignancies. Nivolumab, an immune checkpoint inhibitor directed against programmed death-1, has been approved for non-small cell lung cancer (NSCLC) in pretreated patients. Although it is generally well-tolerated, immunotherapy may be complicated by a wide range of immune-mediated adverse events. We describe the case of an uncommon skin toxicity arising as alopecia universalis induced by nivolumab in a patient with NSCLC. Case description: A 58-year-old man received nivolumab for metastatic NSCLC after progression to 3 lines of chemotherapy. The treatment was prescribed in June 2016, and induced a rapid and significant disease response. Nivolumab was well-tolerated until May 2017, when partial alopecia at hair and eyelashes appeared. In the next months, alopecia became complete and extended to the whole body surface. The dermatologic picture was compatible with alopecia areata. A topical steroid therapy was attempted, without benefit. The patient refused systemic treatments and is still undergoing nivolumab without new toxicities and with persistent disease response. Conclusions: This case suggests that alopecia areata may be a rare immune-related adverse event of immune checkpoint agents. Its late onset in our patient is uncommon and unexpected, underlining that the risk of nivolumab-induced toxicity is not limited to the beginning of treatment. Despite its rarity, alopecia areata should be considered in the range of adverse events potentially induced by immune checkpoint inhibitors even in the long term. Potential association between toxicity and efficacy of immunotherapy in NSCLC warrants further investigation

Interfacing Sca-1pos Mesenchymal Stem Cells with Biocompatible Scaffolds with Different Chemical Composition and Geometry

An immortalized murine mesenchymal stem cell line (mTERT-MSC) enriched for Linneg/Sca-1pos fraction has been obtained through the transfection of MSC with murine TERT and single-cell isolation. Such cell line maintained the typical MSC self-renewal capacity and continuously expressed MSC phenotype. Moreover, mTERT-MSC retained the functional features of freshly isolated MSC in culture without evidence of senescence or spontaneous differentiation events. Thus, mTERT-MSC have been cultured onto PLA films, 30 and 100 μm PLA microbeads, and onto unpressed and pressed HYAFF-11 scaffolds. While the cells adhered preserving their morphology on PLA films, clusters of mTERT-MSC were detected on PLA beads and unpressed fibrous scaffolds. Finally, mTERT-MSC were not able to colonize the inner layers of pressed HYAFF-11. Nevertheless, such cell line displayed the ability to preserve Sca-1 expression and to retain multilineage potential when appropriately stimulated on all the scaffolds tested

Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes

Where the grass is greenest in seagrass seascapes depends on life history and simple species traits of fish

Tropical seagrass meadows are critical habitats for many fish species, yet few studies have investigated the influence of multiple scale-dependent factors and marine protected areas on seagrass fish species of differing life histories. We assessed the influence of fine-scale seagrass meadow characteristics and seascape-scale variables on the abundance of fish in a seagrass-dominated seascape in the Bazaruto Archipelago, Mozambique, particularly examining patterns of nursery- vs. resident species as well as mobile- vs. sedentary species. We found that fish distribution patterns in this seagrass-dominated seascape were dependent on species' life history characteristics; nursery taxa showed lower abundance in seagrass meadows further from adult reef habitats, while resident species within seagrass meadows occurred in higher abundances far from reefs. For taxa utilizing both mangroves and seagrass meadows as nursery habitat, proximity to mangroves was an important factor. Fish abundances were generally influenced by variables at the seascape scale (km), while sedentary species were predominantly influenced by area variables, and smaller seascapes (<500 m in radius) better explained distribution patterns. The influence of marine protected areas was taxon-specific, with the strongest effects of protection on resident species. Our results indicate that protection efforts in seagrass-dominated seascapes can have varying impacts on fish distribution, depending on the life history of the species present, and the geographical placement of the reserve within the seascape. Further, we suggest that simple species attributes can be utilised to describe generalized abundance patterns of fish in seagrass seascapes