Explore the vast range of titles available.

BackgroundPrimary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterised by dysfunction of motile cilia. Ciliary dysmotility causes poor mucociliary clearance and leads to impairment of pulmonary function and severe respiratory infections. PCD has no specific therapy. With the aim to permanently restore gene function and normalise ciliary motility, we used gene editing to replace mutated with wild-type sequence in defective cells.MethodsThe target gene was dynein heavy chain 11 (DNAH11), an essential component of ciliary structure. Airway ciliated cells were collected from two patients with PCD with DNAH11 nonsense mutations and altered ciliary beating and pattern. Repair of the genetic defect was performed ex vivo by site-specific recombination using transcription activator-like effector nucleases (TALENs).ResultsIn an epithelial cell line engineered to contain the DNAH11 target site, TALENs cleaved over 80% of the mutated DNAH11 sequence and replaced the mutated sequence with wild-type sequence in about 50% of cells. In airway ciliated cells of patients with PCD, site-specific recombination and normalisation of ciliary beating and pattern occurred in 33% and 29% of cells, respectively.ConclusionThis study demonstrates that gene editing can rescue ciliary beating ex vivo, opening up new avenues for treating PCD.

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.

Background: An important aspect of managing chronic disorders like bipolar disorder is to have access to relevant health information. This study investigates and compares the quality of information on the treatments of bipolar disorder that is available on English websites, as an international language, and on Italian websites, as a popular local language. Methods: A systematic review search was obtained from four search engines. We excluded unrelated materials, scientific papers, and duplicates. We analyzed popularity with PageRank; technological quality with Nibbler; readability with the Flesh Reading Ease test and Gulpease index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and on the extent of adherence to the HONCode. Results: 35 English and 31 Italian websites were included. The English websites were found to have a higher level of quality information and technological quality than the Italian ones. Overall, the websites were found to be difficult to read, requiring a high level of education. Conclusions: These results can be important to inform guidelines for the improvement of health information and help users to reach a higher level of evidence on the websites. Users should find the benefits of treatment, support for shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing treatment.

Traditional agro-silvo-pastoral systems are becoming each day more important, representing multifunctional systems that can contribute to the preservation of agrobiodiversity and of traditional knowledge and associated culture, to the wellbeing of local communities and to sustainable development of rural areas, as testified by the increasing interest regarding the Globally Important Agricultural Heritage Systems (GIAHS) Programme of the Food and Agriculture Organization (FAO). Despite many researches on traditional agro-silvo-pastoral systems tend to focus only on land uses and land use changes, is also important to analyse the different features that characterize cultural landscapes, as well as to produce detailed spatial maps, in order to preserve and valorise these systems as a whole. The paper intends to compare two traditional silvopastoral systems in two different continents and environments: sabana de morro (El Salvador) and pastures with carob trees (Italy), considered as good example of biocultural diversity. Both these sites are characterized by extensive cattle breeding in a hot climate under the shade of trees, whose fruits can also integrate the animal diet. The study analyzed the traditional landscape structure, with particular attention to the presence of linear elements, that act as property divisions and as ecological corridors, contributing to biodiversity at landscape scale. Sabana de Morro is characterized by a complex system of hedges that enhances the variety of species, while an extensive network of dry-stone walls divides the Sicilian pastures with carob trees. These two different types of linear elements created thanks to the local farmers’ knowledge are made of different materials but can play a similar ecological and social function, acting as a division between one pasture and another, as a delimitation of property boundaries, and are necessary to allow a correct pasture management. Despite the differences, these two traditional linear features deeply characterize the landscape structure and fragmentation, creating important microhabitat for many animal and vegetal species and a network of ecological corridors. For these reasons the conservation of linear features should be promoted at planning level, as well as their restoration. Thanks to the applied methodology, it was possible to identify peculiarities and vulnerabilities of linear features and of the systems as a whole, so that it will be possible to create effective management and conservation tools.

Colorectal cancer (CRC) cells are ‘addicted’ to glutamine to satisfy energy and biosynthetic needs. Inhibiting glutamine metabolism enzymes, like glutaminase, is a potential cancer therapy strategy. Although the GLS inhibitor CB-839 is being evaluated in clinical trials, a comprehensive assessment of its antitumor activity in CRC cells is crucial. The present study aimed to evaluate the impact of CB-839 treatment on different CRC cell lines in terms of survival and proliferation. Furthermore, metabolic adaptations resulting from CB-839 treatment, particularly in energetic pathways, were investigated. Three CRC cell lines (HCT116, HT29, and SW480) were treated with different CB-839 concentrations. Cytotoxicity was assessed via MTT assay, proliferation capacity by flow cytometry, and ATP production rates by Seahorse XF analysis. Moreover, metabolomic profile was explored with untargeted GC-MS and 1 H-NMR, and targeted analysis of the Krebs cycle was conducted using GC-MS/MS. HT29 cells exhibited the highest sensitivity to CB-839. Subsequent experiments focused on HT29 and SW480 cells. CB-839 treatment altered cell cycle progression and increased glycolytic ATP production in HT29 cells. Metabolomic analysis revealed changes in Krebs cycle and glutaminolysis in both cell lines, along with alterations in amino acids, sugars, antioxidants, and organic acid levels. This study highlighted glutamine’s key role in CRC cells and provided a foundation for elucidating the mechanisms of response and resistance to CB-839.

Fibromyalgia (FM) is a chronic and systemic condition that causes widespread chronic pain, asthenia, and muscle stiffness, as well as in some cases depression, anxiety, and disorders of the autonomic system. The exact causes that lead to the development of FM are still unknown today. In a percentage of individuals, the symptoms of FM are often triggered and/or exacerbated by proximity to electrical and electromagnetic devices. Plasma metabolomic profile of 54 patients with fibromyalgia and self-reported electromagnetic sensitivity (IEI-EMF) were compared to 23 healthy subjects using gas chromatography-mass spectrometry (GC–MS) coupled with multivariate statistical analysis techniques. Before the GC–MS analysis the plasma samples were extracted with a modified Folch method and then derivatized with methoxamine hydrochloride in pyridine solution and N-trimethylsilyltrifuoroacetamide. The combined analysis allowed to identify a metabolomic profile able of distinguishing IEI-EMF patients and healthy subjects. IEI-EMF patients were therefore characterized by the alteration of 19 metabolites involved in different metabolic pathways such as energy metabolism, muscle, and pathways related to oxidative stress defense and chronic pain. The results obtained in this study complete the metabolomic \"picture\" previously investigated on the same cohort of IEI-EMF patients with 1 H-NMR spectroscopy, placing a further piece for better understanding the pathophysiological mechanisms in patients with IEI-EMF.

It has long been known that multiple sclerosis (MS) is associated with an increased Epstein-Barr virus (EBV) seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk. This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis, although the mechanisms are debated. This study was designed to assess the prevalence and magnitude of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A) and lytic (BZLF-1, BMLF-1) antigens in relapsing-remitting MS patients (n = 113) and healthy donors (HD) (n = 43) and to investigate whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, lytic antigen-specific CD8+ T cell responses were detected in fewer untreated inactive MS patients than in active MS patients and HD while the frequency of CD8+ T cells specific for EBV lytic and latent antigens was higher in active and inactive MS patients, respectively. In contrast, the CD8+ T cell response to cytomegalovirus did not differ between HD and MS patients, irrespective of the disease phase. Marked differences in the prevalence of EBV-specific CD8+ T cell responses were observed in patients treated with interferon-β and natalizumab, two licensed drugs for relapsing-remitting MS. Longitudinal studies revealed expansion of CD8+ T cells specific for EBV lytic antigens during active disease in untreated MS patients but not in relapse-free, natalizumab-treated patients. Analysis of post-mortem MS brain samples showed expression of the EBV lytic protein BZLF-1 and interactions between cytotoxic CD8+ T cells and EBV lytically infected plasma cells in inflammatory white matter lesions and meninges. We therefore propose that inability to control EBV infection during inactive MS could set the stage for intracerebral viral reactivation and disease relapse.

Cinque Terre, one of the most important Italian cultural landscapes, has not been spared from depopulation and agricultural abandonment processes, that involved many rural areas in Europe, as a consequence of socio-economic transformations that occurred after WWII. Depopulation of rural areas, especially in mountains or in terraced areas, caused significant environmental consequences, such as the decrease of biodiversity, the landscape homogenization, the increase of hydrogeological and forest fires risks. Cinque Terre National Park (5TNP) was established in 1999, and, differently from other Italian National Parks, not just for protecting natural habitats, but mainly to preserve, restore and valorize the historical terraced landscape. Moreover, the area is a UNESCO cultural landscape site and it is partly protected by three Sites of Community Importance. The research intended to investigate the transformations that have affected forested areas inside the 5TNP in the period 1936–2018, also highlighting the connections with hydrogeological and forest fires risks, as a support for the Park planning strategies and the conservation of the UNESCO site. Results highlighted that 37% of the current forests are the consequence of dry stones terraces abandonment that occurred in the twentieth century, with negative effects on the stability of steep slopes, hydrogeological risk, forest fires and on the conservation of a unique cultural landscape. This confirms the current national trend showing no deforestation occurring, but rather a continuous increase of forests on abandoned land. While 5TNP policies and actions are effectively aimed at pursuing an equilibrium between cultivated areas and forests, the Sites of Community Importance located inside the Park mainly focuses on the conservation of “natural habitats”, even if the current vegetation is also the result of secondary successions on former cultivated land. The research highlighted the need to valorize “cultural values” in forest planning as well as the importance of forest history for an accurate planning of forest resources in protected areas.

Mediterranean countries are still characterized by a great variety of historical cultural landscapes, as a result of the millenary human presence that has shaped the territory through agro-silvo-pastoral practices. In the arid regions of south eastern Tunisia, the land use is predominantly olive trees cropping and, because of the difficulties related to water scarcity, local population have developed a peculiar water harvesting technique ensuring the cultivation activities and minimising the risk from droughts. Jessour consist of small dams built across gullies and wadi thalwegs, creating a succession of terraces that partially retain the surface water and sediments required for crop growth. These structures are commonly built inside the watercourses to intercept runoff and sediments or at the foot of slopes. Considering that the biodiversity associated to traditional agricultural practices is important, especially in difficult environments, for ensuring food and nutrition to local communities, it results fundamental to preserve these peculiar practices. Moreover, taking into account that the presence of these water harvesting techniques allows the existence of a wide variety of flora and fauna species it result to be even more important to identify and maintain them from an ecological point of view. The research focused on the jessour identification and mapping in order to define their distribution nearby Douiret, in south of Tunisia, and describe the wide variety of species cultivated thanks to this traditional water harvesting solution. Moreover, using QGis software it was possible to analyse both jessour structure and peculiarities as well as their distribution according to the local morphological structure.