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Cross-taxon congruence, i.e., using certain taxonomic groups as surrogates for others, is receiving growing interest since it may allow decreasing efforts in biodiversity studies. In this work, we investigated the patterns of cross-taxon congruence in species richness and composition between communities of bryophytes, lichens, and vascular plants in different biancana grasslands of a Special Area of Conservation (SAC) of central Italy. We recorded species presence and abundance in 16 plots of 1 × 1 m size and analyzed the data using Procrustes correlation, co-correspondence analysis, and indicator species analysis. We did not highlight any correlation in species richness and composition between the three taxonomic groups. Conversely, the species composition of bryophyte communities was predictive of the species composition of lichen communities. Moreover, lichen richness was negatively correlated with the total cover of vascular plants. Indicator species analysis evidenced the presence of species from the three biotic communities being particularly related, at least at the local scale, to biancana pediments, like the bryophytes Didymodon acutus and Trichostomum crispulum, the lichens Enchylium tenax, Cladonia foliacea, and Psora decipiens, and the vascular plants Brachypodium distachyon, Parapholis strigosa, and Artemisia caerulescens subsp. cretacea. In the biancana pediments, acrocarp mosses, squamulose lichens, therophyte plants and chamaephyte plants coexisted. In spite of the weak cross-taxon congruence between the three taxonomic groups, this study could highlight a locally unique diversity of bryophytes, lichens, and vascular plants related to the extreme environment of biancana pediments, selected by high soil salinity and deposition from the upper eroded slope. Soil erosion and deposition in biancana badlands supports the increase of local multi-taxonomic plant diversity by creating unique ecosystems. Such biodiversity should be considered locally at risk of disappearance, due to the ongoing vanishing of biancana badlands in central Italy.

Objective: Implantation of an endovascular device disrupts the homeostatic CD31:CD31 interactions among quiescent endothelial cells (ECs), platelets, and circulating leukocytes. The aim of this study was to design an endothelial-mimetic coating of nitinol and cobalt-chromium (CoCr) surfaces and stents using synthetic CD31 peptides, to promote device endothelialization and pacific integration within the arterial wall. Methods: Peptides mimicking the domains 1 (D1) and 2 (D2) of CD31 were synthetized and immobilized onto experimental nitinol and CoCr surfaces using a three-step, dip-coating, mussel-inspired protocol using copper-free click chemistry. Human aortic EC phenotype and endothelialization assessment using parallel scratch tests were carried out using five synthetic CD31 peptides coated on 4.8-mm nitinol and CoCr flat disks and were compared with control disks. The CD31 peptide exhibiting the best results in vitro was then immobilized on clinical-grade 3 × 40-mm self-expanding nitinol and 2.5 × 20.0-mm balloon-expandable CoCr stents. Such devices were implanted in native arteries of White New Zealand rabbits, and compared with control uncoated bare metal stents (BMS) and drug-eluting stents 7 and 30 days after implantation using resin cross-sections and scanning electron microscopy (n = 2-3 per group at each time point). Results: Membrane-distal CD31 D1 and D2 peptides exhibited a distinct capability to foster a healthy endothelial phenotype and to promote endothelialization in vitro. By day 7 after implantation, CD31 nitinol and CoCr stents were evenly covered by wholesome ECs, devoid of thromboinflammatory signs, in contrast with both BMS and drug-eluting stents. Such results were consistent until day 30. Conclusions: Membrane-distal CD31 biomimetic peptides seem to camouflage the device surface effectively, preventing local reactions and promoting rapid and seamless endovascular integration. : Clinical Relevance: Despite significant technical advancements, the challenge of vascular stent healing persists. In this preclinical study, we developed a novel endothelial-mimetic coating inspired by the trans-homophilic portion of CD31, a glycoprotein predominantly expressed by endothelial cells and pivotal in circulatory homeostasis. After successive peptide design and surface functionalization, both in vitro and in vivo experiments demonstrated the potential of the CD31-coated surface to promote the acquisition of a physiological endothelial cell phenotype, facilitating rapid healing and peaceful integration of stents. Further studies with larger sample sizes, extended follow-up periods, and assessment of the impact on in-stent restenosis are essential before translating this strategy to clinical applications.

The new species Silene isabellae is described and illustrated from the Skënderbëut mountain range of central Albania. It grows on the ultramafic mountain slopes around Qafë Shtamë, in the understorey of open Pinus nigra forests and in the rocky grasslands above the forest belt, at 1000–1600 m a.s.l. Silene isabellae is a serpentine endemic likely belonging to section Elisanthe (Fenzl ex Endl.) Ledeb. and shows affinities with the widespread European species S. noctiflora L. It is sharply distinct from the latter species in habit, stem and leaf pubescence, morphology, and biology of the flowers and length of the carpophore. Moreover, the ecology of the two taxa is also contrasting, being S. noctiflora a synanthropic-ruderal, mostly in lowlands. Weaker similarities were also observed with the south European subalpine taxa of the group of S. vallesia L. of section Auriculatae (Boiss.) Schischk., though these are not likely to reflect a real systematic affinity.

Abstract Xanthoria parietina (L.) Th. Fr. is a widely spread foliose lichen showing high tolerance against UV-radiation thanks to parietin, a secondary lichen substance. We exposed samples of X. parietina under simulated Martian conditions for 30 days to explore its survivability. The lichen’s vitality was monitored via chlorophyll a fluorescence that gives an indication for active light reaction of photosynthesis, performing in situ and after-treatment analyses. Raman spectroscopy and TEM were used to evaluate carotenoid preservation and possible variations in the photobiont’s ultrastructure respectively. Significant differences in the photo-efficiency between UV irradiated samples and dark-kept samples were observed. Fluorescence values correlated with temperature and humidity day-night cycles. The photo-efficiency recovery showed that UV irradiation caused significant effects on the photosynthetic light reaction. Raman spectroscopy showed that the carotenoid signal from UV exposed samples decreased significantly after the exposure. TEM observations confirmed that UV exposed samples were the most affected by the treatment, showing chloroplastidial disorganization in photobionts’ cells. Overall, X. parietina was able to survive the simulated Mars conditions, and for this reason it may be considered as a candidate for space long-term space exposure and evaluations of the parietin photodegradability.

Abstract Despite beneficial effects in acute heart failure, the full therapeutic potential of recombinant relaxin-2 has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. A multiparametric optimization of the relaxin B-chain led to the identification of single chain lipidated peptide agonists of RXFP1 like SA10SC-RLX with subcutaneous bioavailability and extended half-life. SA10SC-RLX has sub nanomolar activity on cells expressing human RXFP1 and molecular modeling associated with the study of different RXFP1 mutants was used to decipher the mechanism of SA10SC-RLX interaction with RXFP1. Telemetry was performed in rat where SA10SC-RLX was able to engage RXFP1 after subcutaneous administration without tachyphylaxis after repeated dosing. Renal blood flow was then used as a translational model to evaluate RXFP1 activation. SA10SC-RLX increased renal blood flow and decreased renal vascular resistance in rats as reported for relaxin in humans. In conclusion, SA10SC-RLX mimics relaxin activity in in vitro and in vivo models of acute RXFP1 engagement. SA10SC-RLX represents a new class of long-lasting RXFP1 agonist, suitable for once daily subcutaneous administration in patients and potentially paving the way to new treatments for chronic fibrotic and cardiovascular diseases.

In this contribution, new data concerning bryophytes, fungi and lichens of the Italian flora are presented. It includes new records and confirmations for the algal genus Chara, for the bryophyte genera Bryum, Grimmia, Cephaloziella, Hypnum, Nogopterium, Physcomitrium, Polytrichastrum, Rhynchostegiella, Saelania, and Schistostega, the fungal genera Cortinarius, Lentinellus, Omphalina, and Xerophorus, and the lichen genera Acarospora, Agonimia, Candelariella, Cladonia, Graphis, Gyalolechia, Hypogymnia, Lichinella, Megalaria, Nephroma, Ochrolechia, Opegrapha, Peltigera, Placidium, Ramalina, Rhizoplaca, Ropalospora, Strangospora, Toniniopsis, Usnea, and Zahlbrucknerella.

Lobaria pulmonaria (L.) Hoffm. is a tripartite, broad-lobed foliose lichen usually found on bark and on epiphytic and epilithic mosses in humid forests. Currently, the species is threatened in most European countries because of its sensitivity to environmental alterations. In this paper, a total of 107 previous studies across more than 50 years were analysed to gain insight into the multiple roles that L. pulmonaria plays in forest habitats, specifically relating to ecosystem services and as environmental bioindicator. Content analysis was employed to systematically characterise and classify the existing papers on the functions performed by L. pulmonaria into several groups mostly based on research topic and scope. Two main types of ecosystem services (N2 fixation and feeding) offered by L. pulmonaria have been identified, with varying research aims and types of parameters measured in the studies. Two aspects of current biomonitoring applications using L. pulmonaria in forest habitats (concerning atmospheric pollution and forest management) were analysed, and it was found that the number of related studies increased significantly in recent years. Finally, the current practices of monitoring using L. pulmonaria as a biological indicator are discussed, and recommendations are provided.

The excessive use of chemical fertilizers and pesticides in agriculture is increasing the demand for novel products to improve the quality of crops in a more sustainable way. Wood distillate (WD, pyroligneous acid) is a by-product obtained during the pyrolysis of plant biomass that can be successfully applied in agriculture due to its ability to enhance the growth, size, and weight of edible plant parts. However, there is little information concerning its plant yield-promoting effects on leguminous crops. The present work investigated the effects of WD on the yield, protein content and mineral composition of chickpea (Cicer arietinum L.), lentil (Lens culinaris L.) and bean (Phaseolus vulgaris L.) plants grown in field conditions. The application of WD showed remarkable yield-promoting effects mostly in lentil plants, which significantly increased plant and shoot biomass, the number and weight of both pods and seeds, as well as the total seed protein content. Furthermore, seeds from WD-treated plants differentially increased the concentration of elements with high nutritional value for human health, including Fe, Ca, Mg and K. These results suggest that the effects of WD among the legumes tested are species-specific and that WD could be an optimal candidate to grow high-yielding legumes with improved seed nutritional quality.

Lichens are poikilohydric organisms, whose internal water content tends to reflect external humidity conditions. After drying, they can reactivate their metabolic activity through water vapor uptake or liquid water input. Thus, lichen water-related functional traits are important as they are involved in the duration of the hydrated period. Models predicting the effect of environmental conditions on lichens are based mainly on the presence or absence of adult thalli. Nevertheless, ecological conditions required by lichens might vary during their life cycle, for example during propagule establishment or in the first stages of thallus development. Little is known about the different ecological requirements at the different development stages in lichens. In this work, we measured water holding capacity (WHC) and specific thallus mass (STM) of adult and juvenile thalli of the model species Lobaria pulmonaria along a climatic gradient to constrain the process-based model LiBry. The LiBry model allows accounting for the productivity of lichens with different physiological strategies under various environmental conditions. We simulated the activity and performance of adult and juvenile thalli in 9 regions of Italy and Corsica. The model was used to test if adult thalli of L. pulmonaria have a higher survival probability due to their higher aerodynamic resistance. In the current climatic condition, the LiBry model predicts a higher survival probability of adults with decreasing absolute survival rates of both life stages with increasing temperature. Adult thalli also result in having higher active time, STM, and relative growth rate (RGR). We discuss the main implications of our simulation outputs, provide future perspectives and possible implementations of the LiBry model.

In this contribution, new data concerning bryophytes, fungi, and lichens of the Italian flora are presented. It includes new records and confirmations for the bryophyte genera Aneura, Aulacomnium, Dumortiera, Fossombronia, Hennediella, Hygrohypnella, Pohlia, Porella, Riccardia, Tortella, and Tortula, the fungal genera Cortinarius, Mycena, Naucoria, Trichoglossum, and Tubaria and the lichen genera Agonimia, Blastenia, Chaenotheca, Cladonia, Endocarpon, Gyalecta, Lecanographa, Parmeliella, Porpidia, Stenhammarella, and Thelidium.

The botanical exploration of the Majella National Park has a long tradition dating back to the eighteenth century. However, the lichen biota of this area is still poorly investigated. To provide a baseline for future investigations, in this annotated checklist, we summarised all available information on the occurrence of lichens in the Majella National Park, retrieved from previous literature, herbarium material and original data produced by recent research. The checklist includes 342 infrageneric taxa. However, seven taxa are considered as dubious, thus setting the number of accepted taxa at 335, i.e. 45.8% of those currently known to occur in the Abruzzo Region. This checklist provides a baseline of the lichens known to occur in the Majella National Park, highlighting the potential of this area as a hotspot of lichen biodiversity, especially from a biogeographical point of view as indicated by the occurrence of several arctic-alpine species that form disjunct populations in the summit area of the massif.

In this contribution, new data concerning red algae, bryophytes, fungi and lichens of the Italian flora are presented. It includes new records and confirmations for the algal genus Thorea, for the bryophyte genera Ephemerum, Hedwigia, Pogonatum, Riccia, Sphagnum, and Tortella, the fungal genera Pileolaria and Sporisorium, and the lichen genera Bacidia, Cerothallia, Chaenotheca, Cladonia, Halecania, Lecanora, Phylloblastia, Physcia, Protoparmelia, Pycnora, Segestria, and Sphaerophorus.

In this contribution, new data concerning algae, bryophytes, fungi, and lichens of the Italian flora are presented. It includes new records and confirmations for the algae genus Chara, the bryophyte genera Homalia, Mannia, and Tortella, the fungal genera Cortinarius, Russula, and Stereum, and the lichen genera Cetrelia, Cladonia, Enterographa, Graphis, Lecanora, Lepraria, Multiclavula, Mycomicrothelia, Parmelia, Peltigera, Pleopsidium, Psora, Scytinium, Umbilicaria, and Rhizocarpon.

The master transcription factor RORγt, encoded by the RORC gene, controls the polarization of CD4+ T cells expressing interleukin-17 (Th17). Here the authors describe several regulatory elements at the RORC locus that are recognized by NFAT and NFkB to induce a permissive epigenetic configuration of the RORC gene for RORγt expression and Th17 differentiation.

Microclimatic conditions are important in determining lichen distribution at small scale, and may determine whether the species persist when the surrounding environmental conditions have drastically changed. This is the case with forest management, since a sudden variation of microclimatic conditions (increase of solar radiation, temperature, wind and a reduction of humidity) may occur after logging. In this study, the combined effect of forest logging and microclimatic conditions on the growth probabilities and growth rates of the model species Lobaria pulmonaria was assessed in mixed oak stands. To this purpose, 800 fragments of L. pulmonaria (L. pulmonaria populations in logged forests.

In this contribution, new data concerning bryophytes, fungi, and lichens of the Italian flora are presented. It includes new records and confirmations for the bryophyte genera Diplophyllum and Ptychostomum, the fungal genera Arrhenia, Gymnosporangium, and Sporidesmium and the lichen genera Arthonia, Coenogonium, Flavoplaca, Gyalolechia, Parmotrema, Peltigera, Pterygiopsis, Squamarina, Tornabea, and Waynea.

The aim of this study was to investigate the ability of biochar amendment to reduce the availability of Pb in the soil and its uptake in lettuce (Lactuca sativa L. var. adela). Seedlings of lettuce were cultivated in Pb-contaminated soils, both with and without 5% biochar (w/w), as well as in a simplified soilless system (hydroponics) at the ecologically relevant Pb concentration of 100 µM, both with and without 1% biochar. Soils amended with biochar resulted in a ca. 50% reduction of the extractable (bioavailable) fraction of Pb, limiting the accumulation of this toxic element in the leaves of lettuce by ca. 50%. A similar behavior was observed for lettuce plants grown hydroponically, even with a much higher reduction of Pb uptake (ca. 80%). Increased cation exchange capacity and pH were likely the main factors limiting the bioavailability of Pb in the soil. Complexation with functional groups and precipitation/co-precipitation both on the biochar surface and in soil aggregates were likely the main mechanisms immobilizing this element.

Immune-mediated inflammatory diseases (IMIDs), such as spondyloarthritis (SpA), psoriasis, Crohn's disease (CD), and rheumatoid arthritis (RA) remain challenging illnesses. They often strike at a young age and cause lifelong morbidity, representing a considerable burden for the affected individuals and society. Pioneering studies have revealed the presence of a TNF-dependent proinflammatory cytokine cascade in several IMIDs, and the introduction of anti-TNF therapy 20 years ago has proven effective to reduce inflammation and clinical symptoms in RA, SpA, and other IMID, providing unprecedented clinical benefits and a valid alternative in case of failure or intolerable adverse effects of conventional disease-modifying antirheumatic drugs (DMARDs, for RA) or non-steroidal anti-inflammatory drugs (NSAIDs, for SpA). However, our understanding of how TNF inhibitors (TNFi) affect the immune system in patients is limited. This question is relevant because anti-TNF therapy has been associated with infectious complications. Furthermore, clinical efficacy of TNFi is limited by a high rate of non-responsiveness (30–40%) in RA, SpA, and other IMID, exposing a substantial fraction of patients to side-effects without clinical benefit. Despite the extensive use of TNFi, it is still not possible to determine which patients will respond to TNFi before treatment initiation. The recent introduction of antibodies blocking IL-17 has expanded the therapeutic options for SpA, as well as psoriasis and psoriatic arthritis. It is therefore essential to develop tools to guide treatment decisions for patients affected by SpA and other IMID, both to optimize clinical care and contain health care costs. After a brief overview of the biology of TNF, its receptors and currently used TNFi in the clinics, we summarize the progress that has been made to increase our understanding of the action of TNFi on the immune system in patients. We then summarize efforts dedicated to identify biomarkers that can predict treatment responses to TNFi and we conclude with a section dedicated to the recently introduced inhibitors of IL-17A and IL-23 in SpA and related diseases. The focus of this review is on SpA, however, we also refer to RA on topics for which only limited information is available on SpA in the literature.

Assessing the ecological impacts of environmental change on biological communities requires knowledge of the factors driving the spatial patterns of the three diversity facets along extensive environmental gradients. We quantified the taxonomic (TD), functional (FD), and phylogenetic diversity (PD) of lichen epiphytic communities in 23 beech forests along Europe to examine their response to environmental variation (climate, habitat quality, spatial predictors) at a continental geographic scale. We selected six traits related to the climatic conditions in forest ecosystems, the water-use strategy and the nutrient uptake, and we built a phylogenetic tree based on four molecular markers. FD and climate determined TD and PD, with spatial variables also affecting PD. The three diversity facets were primarily shaped by distinct critical predictors, with the temperature diurnal range affecting FD and PD, and precipitation of the wettest month determining TD. Our results emphasize the value of FD for explaining part of TD and PD variation in lichen communities at a broad geographic scale, while highlighting that these diversity facets provide complementary information about the communities’ response under changing environmental conditions. Furthermore, traits such as growth form, photobiont type, and reproductive strategy mediated the response of lichen communities to abiotic factors emerging as useful indicators of macroclimatic variations.

Forest logging can be detrimental for non-vascular epiphytes, determining the loss of key components for ecosystem functioning. Legal logging in a Mediterranean mixed oak forest (Tuscany, Central Italy) in 2016 heavily impacted sensitive non-vascular epiphytes, including a large population of the threatened forest lichen Lobaria pulmonaria (L.) Hoffm. This event offered the background for this experiment, where the potential effects of logging in oak forests are simulated by means of L. pulmonaria micro-transplants (thallus fragments Quercus cerris), half in a logged and half in an unlogged stand. Chlorophyll (Chl) a fluorescence emission and total chlorophyll content are used as a proxy for the overall vitality of the transplants, while their growth is considered an indicator of long-term effects. Generally, vitality and growth of the transplants in the logged stand are lower than in the unlogged stand. Both vitality and growth vary between the meristematic and non-meristematic fragments, the former performing much better. Hence, irrespective of forest management, meristematic fragments show higher growth rates (0.16–0.18 cm2 year−1) than non-meristematic ones (0.02–0.06 cm2 year−1). Considering that a conservation-oriented management for this species should be tailored at the habitat-level and, especially, at the tree-level, our results suggest that for appropriate conservation strategies, it is necessary to consider the life cycle of the lichen, since the probability of survival of the species may vary, with meristematic fragments having more chance to survive after logging.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND:We performed a qualitative study to investigate the experiences of participants in a multicentre randomized controlled trial on a home-based palliative approach (HPA) for adults with severe multiple sclerosis (MS) and their caregivers. Our aim was to explore the strengths and challenges of the intervention, and circumstances that may have influenced its efficacy. METHODS:Participants to the qualitative study were the patients, their caregivers, patient referring physicians, and the teams who delivered the HPA intervention. We performed semi-structured one-on-one interviews with 12 patients and 15 informal caregivers chosen using a maximum variation strategy, two focus group meetings with patient referring physicians (4 participants each), and one with the HPA teams (9 participants). RESULTS:From data analysis (framework method) 38 sub-categories emerged, which were grouped into 10 categories and 3 themes: 'expectations,' 'met and unmet needs', and 'barriers'. Intervention benefits were improved control of symptoms and reduced sense of isolation of the patient-caregiver dyads. Limitations were: factors related to experimental design (difficulty of dyads in identifying examiner and team roles, additional burden for caregivers); team issues (insufficient team building /supervision, competing priorities); limitations of the intervention itself (insufficient length, lack of rehabilitation input); and external factors (resource limitations, under-responsive services/professionals). The referring physician focus groups provided little experiential data. CONCLUSIONS:The HPA reduced patient symptoms and sense of isolation in patients and caregivers. The indirect role of the HPA teams, and insufficient length of the intervention were key limitations. The experimental design imposed additional burdens on the dyads. Key barriers were the paucity of available services, the demanding administrative procedures, and lack of networking facilities. These findings suggest that two major requirements are necessary for home palliative care to be effective in this patient population: HPA teams well-connected with MS rehabilitation services, and care delivered over the long-term, with variable intensity. TRIAL REGISTRATION:Current Controlled Trials ISRCTN73082124 (Registered 19/06/2014).

We previously demonstrated that RanBP9 overexpression increased Aβ generation and amyloid plaque burden, subsequently leading to robust reductions in the levels of several synaptic proteins as well as deficits in the learning and memory skills in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin-immunoreactive puncta (52%, p

The interpretation of lichen bioaccumulation data is of paramount importance in environmental forensics and decision-making processes. By implementing basic ideas underlying previous interpretative scales, new dimensionless, species-independent “bioaccumulation scales” for native and transplanted lichens are proposed. Methodologically consistent element concentration datasets were populated with data from biomonitoring studies relying on native and transplanted lichens. The scale for native lichens was built up by analyzing the distribution of ratios between element concentration data and species-specific background concentration references (B ratios), herein provided for Flavoparmelia caperata and Xanthoria parietina (foliose lichens). The scale for transplants was built up by analyzing the distribution of ratios between element concentration in exposed and unexposed samples (EU ratio) of Evernia prunastri and Pseudevernia furfuracea (fruticose lichens). Both scales consist of five percentile-based classes; namely, “Absence of”, “Low”, “Moderate”, “High”, and “Severe” bioaccumulation. A comparative analysis of extant interpretative tools showed that previous ones for native lichens suffered from the obsolescence of source data, whereas the previous expert-assessed scale for transplants failed in describing noticeable element concentration variations. The new scales, based on the concept that pollution can be quantified by dimensionless ratios between experimental and benchmark values, overcome most critical points affecting the previous scales.

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.

Few data on services for people with severe multiple sclerosis (MS) are available. The Palliative Network for Severely Affected Adults with MS in Italy (PeNSAMI) developed a home palliative care program for MS patients and carers, preceded by a literature review and qualitative study (here reported).To identify unmet needs of people with severe MS living at home by qualitative research involving key stakeholders, and theorize broad areas of intervention to meet those needs.Data were collected from: at least 10 personal interviews with adults with severe MS (primary/secondary progressive, EDSS≥8.0); three focus group meetings (FGs) of carers of people with severe MS; and two FGs of health professionals (HPs). Grounded theory guided the analysis of interview and FG transcripts, from which the areas of intervention were theorized.Between October 2012 and May 2013, 22 MS patients, 30 carers and 18 HPs participated. Forty-eight needs themes were identified, grouped into 14 categories and four domains. Seven, highly interdependent intervention areas were theorized. Patients had difficulties expressing needs; experiences of burden and loneliness were prominent, chiefly in dysfunctional, less affluent families, and among parent carers. Needs differed across Italy with requirements for information and access to services highest in the South. All participants voiced a strong need for qualified personnel and care coordination in day-to-day home care. Personal hygiene emerged as crucial, as did the need for a supportive network and preservation of patient/carer roles within family and community.Unmet needs transcended medical issues and embraced organizational and psychosocial themes, as well as health policies. The high interdependence of the seven intervention areas theorized is in line with the multifaceted approach of palliative care. At variance with typical palliative contexts, coping with disability rather than end-of-life was a major concern of patients and carers.

RanBP9 is known to act as a scaffolding protein bringing together a variety of cell surface receptors and intracellular targets thereby regulating functions as diverse as neurite and axonal outgrowth, cell morphology, cell proliferation, myelination, gonad development, myofibrillogenesis and migration of neuronal precursors. Though RanBP9 is ubiquitously expressed in all tissues, brain is one of the organs with the highest expression levels of RanBP9. In the neurons, RanBP9 is localized mostly in the cytoplasm but also in the neurites and dendritic processes. We recently demonstrated that RanBP9 plays pathogenic role in Alzheimer's disease. To understand the role of RanBP9 in the brain, here we generated RanBP9 null mice by gene-trap based strategy. Most of Ran-/- mice die neonatally due to defects in the brain growth and development. The major defects include smaller cortical plate (CP), robustly enlarged lateral ventricles (LV) and reduced volume of hippocampus (HI). The lethal phenotype is due to a suckling defect as evidenced by lack of milk in the stomachs even several hours after parturition. The complex somatosensory system which is required for a behavior such as suckling appears to be compromised in Ran-/- mice due to under developed CP. Most importantly, RanBP9 phenotype is similar to ERK1/2 double knockout and the neural cell adhesion receptor, L1CAM knockout mice. Both ERK1 and L1CAM interact with RanBP9. Thus, RanBP9 appears to control brain growth and development through signaling mechanisms involving ERK1 and L1CAM receptor.