413 research outputs found

    Sars‐cov‐2 pandemic: Not the first, not the last

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    The common trait among the betacoronaviruses that emerged during the past two decades (the severe acute respiratory syndrome coronavirus—SARS‐CoV, the Middle East respiratory syndrome coronavirus—MERS‐CoV, and the recent SARS coronavirus 2—SARS‐CoV‐2) is their probable animal origin, all deriving from viruses present in bat species. Bats have arisen the attention of the scientific community as reservoir of emerging viruses, given their wide geographical distribution, their biological diversity (around 1,400 species, 21 different families and over 200 genera), and their peculiar ecological and physiological characteristics which seem to facilitate them in harbouring a high viral diversity. Several human activities may enable the viral spill‐over from bats to humans, such as deforestation, land‐use changes, increased livestock grazing or intensive production of vegetal cultures. In addition, the globalization of trade and high global human mobility allow these viruses to be disseminated in few hours in many parts of the World. In order to avoid the emergence of new pandemic threats in the future we need to substantially change our global models of social and economic development, posing the conservation of biodiversity and the preservation of natural ecosystems as a pillar for the protection of global human health

    Demolishing or Renovating? Life Cycle Analysis in the Design Process for Building Renovation: The ProGETonE Case

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    It is well known that a large part of the existing European building stock needs to be renovated to increase structural and energy performance. Unfortunately, deep renovations come with high ini-tial costs, and therefore, owners and real estate developers often prefer complete demolition and reconstruction. Both options depend on specific factors, and to select which option could be the closest to the optimal scenario, it is necessary to evaluate all environmental, social, and economic indicators. Life Cycle Analysis is of great significance to evaluate building sustainability, in partic-ular through the comparison between different design alternatives. However, the life cycle impacts of the construction stage depend on selected materials and technologies that can be subject to change during the subsequent stages of the design process, i.e., moving from preliminary design to detailed design and execution plans. With the aim of understanding the role of LCA during the design process, the case study of “ProGETonE—Proactive Synergy of Integrated Efficient Tech-nologies on Buildings’ Envelopes” has been addressed, leading to the observation that the impacts, in particular the global warming potential (GWP), raised significantly. Building Information Mod-elling (BIM) helped the information sharing and management of this project, which consists of the deep renovation and architectural reshaping of an existing student residence through the con-struction of integrated façade systems

    International Network for Capacity Building for the Control of Emerging Viral Vector-Borne Zoonotic Diseases: Arbo-Zoonet

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    Arboviruses are arthropod-borne viruses, which include West Nile fever virus (WNFV), a mosquito-borne virus, Rift Valley fever virus (RVFV), a mosquito-borne virus, and Crimean-Congo haemorrhagic fever virus (CCHFV), a tick-borne virus. These arthropod-borne viruses can cause disease in different domestic and wild animals and in humans, posing a threat to public health because of their epidemic and zoonotic potential. In recent decades, the geographical distribution of these diseases has expanded. Outbreaks of WNF have already occurred in Europe, especially in the Mediterranean basin. Moreover, CCHF is endemic in many European countries and serious outbreaks have occurred, particularly in the Balkans, Turkey and Southern Federal Districts of Russia. In 2000, RVF was reported for the first time outside the African continent, with cases being confirmed in Saudi Arabia and Yemen. This spread was probably caused by ruminant trade and highlights that there is a threat of expansion of the virus into other parts of Asia and Europe. In the light of global warming and globalisation of trade and travel, public interest in emerging zoonotic diseases has increased. This is especially evident regarding the geographical spread of vector-borne diseases. A multi-disciplinary approach is now imperative, and groups need to collaborate in an integrated manner that includes vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions

    Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation

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    Multiple myeloma (MM) has benefited from significant advancements in treatment that have improved outcomes and reduced morbidity. However, the disease remains incurable and is characterized by high rates of drug resistance and relapse. Consequently, methods to select the most efficacious therapy are of great interest. Here we utilize a functional assay to assess the ex vivo drug sensitivity of single multiple myeloma cells based on measuring their mass accumulation rate (MAR). We show that MAR accurately and rapidly defines therapeutic susceptibility across human multiple myeloma cell lines to a gamut of standard-of-care therapies. Finally, we demonstrate that our MAR assay, without the need for extended culture ex vivo, correctly defines the response of nine patients to standard-of-care drugs according to their clinical diagnoses. This data highlights the MAR assay in both research and clinical applications as a promising tool for predicting therapeutic response using clinical samples

    CDKN1A upregulation and cisplatin-pemetrexed resistance in non-small cell lung cancer cells

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    Cisplatin-pemetrexed is a frequently adopted first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) ineligible for biological therapy, notwithstanding its limited efficacy. In the present study, the RAL cell line, an epidermal growth factor receptor (EGFR)-wild-type, p53- and KRAS-mutated model of NSCLC, was used to investigate novel biomarkers of resistance to this treatment. Cells were analyzed 96 h (96 h-post wo) and 21 days (21 days-post wo) after the combined treatment washout. Following an initial moderate sensitivity to the treatment, the cell growth proliferative capability had fully recovered. Gene expression analysis of the resistant surviving cells revealed a significant upregulation of CDKN1A expression in the cells at 96-h post-wo and, although to a lesser extent, in the cells at 21 days-post wo, accompanied by an enrichment of acetylated histone H3 in its promoter region. CDKN1A was also upregulated at the protein level, being mainly detected in the cytoplasm of the cells at 96 h-post wo. A marked increase in the number of apoptotic cells, together with a significant G1 phase block, were observed at 96-h post wo in the cells in which CDKN1A was knocked down, suggesting its involvement in the modulation of the response of RAL cells to the drug combination. On the whole, these data suggest that CDKN1A plays a role in the response to the cisplatin-pemetrexed combination in advanced KRAS-mutated NSCLC, thus suggesting that it may be used as a promising predictive marker

    A proposed design for the evaluation of change in a small reference group.

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    Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets

    Techniques, Tricks, and Stratagems of Oral Cavity Computed Tomography and Magnetic Resonance Imaging

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    The oral cavity constitutes a complex anatomical area that can be affected by many devel-opmental, inflammatory, and tumoural diseases. MultiSlice Computed Tomography (MSCT) and Magnetic Resonance Imaging (MRI) currently represent the essential and complementary imaging techniques for detecting oral cavity abnormalities. Advanced MRI with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced perfusion-weighted imaging (DCE-PWI) has recently increased the ability to characterise oral lesions and distinguish disease recurrences from post therapy changes. The analysis of the oral cavity area via imaging techniques is also complicated both by mutual close appositions of different mucosal surfaces and metal artifacts from dental materials. Nevertheless, an exact identification of oral lesions is made possible thanks to dynamic manoeuvres and specific stratagems applicable on MSCT and MRI acquisitions. This study summarises the currently available imaging techniques for oral diseases, with particular attention to the role of DWI, DCE-PWI, and dynamic manoeuvres. We also propose MSCT and MRI acquisition protocols for an accurate study of the oral cavity area
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