Histamine regulates actin cytoskeleton in human toll-like receptor 4-activated monocyte-derived dendritic cells tuning CD4+ T lymphocyte response

Histamine, a major mediator in allergic diseases, differentially regulates the polarizing ability of dendritic cells after Toll-like receptor (TLR) stimulation, by not completely explained mechanisms. In this study we investigated the effects of histamine on innate immune reaction during the response of human monocyte-derived DCs (mDCs) to different TLR stimuli: LPS, specific for TLR4, and Pam3Cys, specific for heterodimer molecule TLR1/TLR2. We investigated actin remodeling induced by histamine together with mDCs phenotype, cytokine production, and the stimulatory and polarizing ability of Th0. By confocal microscopy and RT-PCR expression of Rac1/CdC42 Rho GTPases, responsible for actin remodeling, we show that histamine selectively modifies actin cytoskeleton organization induced by TLR4, but not TLR2 and this correlates with increased IL4 production and decreased IFNγ by primed T cells. We also demonstrate that histamine-induced cytoskeleton organization is at least in part mediated by down-regulation of small Rho GTPase CdC42 and the protein target PAK1, but not by down-regulation of Rac1. The presence and relative expression of histamine receptors HR1–4 and TLRs were determined as well. Independently of actin remodeling, histamine down-regulates IL12p70 and CXCL10 production in mDCs after TLR2 and TLR4 stimulation. We also observed a trend of IL10 up-regulation that, despite previous reports, did not reach statistical significance

High results and lower cost in four-bone arthrodesis with retrograde screws

Aim To describe the technique of the four-corner fusion with two retrograde crossed headless screws in cases of carpal collapse. Methods This technique is a consolidated procedure performed in cases of scaphoid non- union advanced collapse (SNAC) type II and III, scapholunate advanced collapse (SLAC) type II and III and in other cases of carpal collapse. Between 2017 and 2019 we treated six male patients (a mean age of 55.0 years) with radiocarpal osteoarthritis. Our technique involves the use of two retrograde crossed headless screws; the first screw was placed distally proximally from the uncinate to the lunate and the second screw from the pyramidal to the capitate, crossed at approximately 90 degrees. Clinical and radiographic two-year follow-up was performed. Before the treatment and during the follow-ups VAS, PRWE and DASH Quick score scales, measured wrist range of motion (WROM) were administered and evaluated. Results In all cases the X-ray consolidation of arthrodesis within five months was noticed; in 50% patients already under 3-month control. No observed signs of mobilization of screws and inflammatory or infectious processes were found. All patients were satisfied (reduction/disappearance of pain). All surgically treated patients resumed normal daily activities. These improvements were confirmed by the results of the evaluation scale and clinical examination. Conclusion This technique, in our opinion, represents a gold standard. Its low costs of the material used (especially comparing to other technique), a low prevalence of complications of materials and fusion in 100% of cases should be also considered

Alternative source of stem cells derived from human periodontal ligament: a new treatment for experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is categorized as an autoimmune disease and is potentially one of the most common causes of neurological disability in young adults. Formation of the sclerotic plaques of which the disease gets its name represents the end stage of a process involving inflammation, demyelination and remyelination, oligodendrocytes depletion, and astrogliosis as well as neuronal and axonal degeneration (1). MS damages the central nervous system and leads to a disabling condition. Recently, the potential role of mesenchymal stem cells (MSCs), derived in promoting tissue repair and disease control has been investigated by using an experimental autoimmune encephalomyelitis (EAE) model (2). The objective of the research was to investigate the product effects by mesenchymal stem cells derived from human periodontal ligament (hPDLSCs) when administered in an experimental model of autoimmune encephalomyelitis (EAE). EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in C57BL/6 mice. Then, mice were observed every 48 hours for signs of EAE and weight loss. At the onset of disease, approximately 14 days after immunization, EAE mice were subjected to a single intravenous injection of hPDLSCs (10(6) cells/150 μl) into the tail vein. At the point of animal sacrifice on day 56 after EAE induction, spinal cord and brain tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis. Obtained results reveal that treatment with hPDLSCs may produce neuroprotective effects against EAE, diminishing both clinical signs and histological score typical of the disease (lymphocytic infiltration and demyelination) probably through the production of neurotrophic factors (results focused on brain-derived neurotrophic factor and nerve growth factor expression). Furthermore, administration of hPDLSCs modulates expression of inflammatory key markers (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, glial fibrillary acidic protein, Nrf2 and Foxp3), the release of CD4 and CD8α T cells, and the triggering of apoptotic death pathway (data shown for cleaved caspase 3, p53 and p21). In light of the achieved results, transplantation of hPDLSCs may represent a putative novel and helpful tool for multiple sclerosis treatment. These cells could have considerable implication for future therapies for multiple sclerosis and this study may represent the starting point for further investigations

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the "adaptive" NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation

ClimateFish: A Collaborative Database to Track the Abundance of Selected Coastal Fish Species as Candidate Indicators of Climate Change in the Mediterranean Sea

Under the effects of global warming, many animals and plants are undergoing rapid distribution shifts. These changes can be particularly rapid in marine fishes, and many species have responded markedly to recent increases in sea temperature. ClimateFish is an open-access database, which collates abundance data for 7 Mediterranean indigenous and 8 non-indigenous fishes, proposed as candidate indicators of climate change. These species have been selected by a network of Mediterranean scientists based on their wide distribution, responsiveness to temperature conditions and easy identification. Data are periodically collected according to a standard visual census protocol in four different depth layers. At present, the database collates data on a total number of 101'771 observed individuals belonging to the 15 target species. Counts were realized along 3142 transects carried out in 7 Mediterranean countries between 2009 and 2021. This database, associated with climate data, offers new opportunities to investigate spatiotemporal effects of climate change and to test the effectiveness of each selected indicator. Data are available at https://doi.org/10.17882/86784.The Mediterranean ClimateFish initiative was initially conceived by the international basin wide monitoring program CIESM Tropical Signals (funded by the Albert II of Monaco Foundation) and subsequently supported by the Interreg Med Programme (Projects: MPA-ADAPT, grant number 1MED15_3.2_M2_337 and MPA Engage, grant number 5MED18_3.2_M23_007), 85% co funded by the European Regional Development Fund

How do basic human values affect self-care of type 2 diabetes patients? A multicentre observational study

In type 2 diabetes mellitus (T2DM) patients, human values have been identified as having a possible impact on self-care. Despite this, basic human values have never been described in the T2DM population and the association between basic human values and self-care has not been assessed. The aims of this study were to describe basic human values and self-care, and investigate the associations between basic human values and self-care in adults with T2DM. The study was cross-sectional multicentre with T2DM patients (n = 390). Sociodemographic and clinical data were collected from charts, and two questionnaires were administered. The Portrait Values Questionnaire (PVQ) measured basic human values and allowed us to group patients into four groups based on the value profile: (A) Openness to Change and Self-Transcendence, (B) Conservation and Self-Transcendence, (C) Conservation and Self-Enhancement, and (D) Openness to Change and Self-Enhancement. The Self-care of Diabetes Inventory measured self-care maintenance, self-care monitoring, self-care management, and self-care confidence, according to the Middle-Range Theory of Self-Care of Chronic Illness. Multiple regression models were used to assess associations between the basic human values and self-care. Group D (Openness to Change and Self-Enhancement) performed significantly lower self-care maintenance (p = .024) and self-care monitoring (p = .031) when compared with Group A, and lower self-care monitoring (p = .008) and self-care management (p = .018) when compared with Group B. Group D showed significantly lower self-care monitoring (p = .027) when compared with Group C. People with T2DM who value more self-enhancement and openness to change might be more prone to perform worse self-care compared with those who value conservation and self-transcendence. Clinicians should consider this when designing interventions aimed at improving self-care behaviors in patients with T2DM

Socio-demographic and clinical determinants of self-care in adults with type 2 diabetes: A multicentre observational study

Aims To describe self-care as defined by the Middle Range Theory of Self-Care of Chronic Illness and to identify clinical and socio-demographic determinants in a T2DM population. Methods A multicentre observational cross-sectional study was conducted involving 540 adults with a confirmed diagnosis of T2DM from six outpatient diabetes services in Italy. Socio-demographic and clinical data were collected from medical records. The Self-Care of Diabetes Inventory (SCODI) was used to measure self-care maintenance, monitoring, management, and confidence dimensions. For each separate scale, scores were standardized 0–100 with higher SCODI scores indicating better self-care; a score ≥ 70 is adequate. Multiple quantile regression models were performed to identify determinants of each self-care dimension. Results Self-care maintenance (median = 81.3) and self-care confidence (median = 79.5) were adequate in most of the subjects. Self-care monitoring was adequate in only half of the sample (median = 70.6). Self-care management was poor (median = 59.4). Lower self-care maintenance was associated with lower self-care confidence (p < 0.001). Lower self-care monitoring was associated with being male (p < 0.001), having lower self-care confidence (p < 001), and having diabetes for < 10 years (p < 0.001). Lower self-care management was associated with being male (p = 0.002), being older (p = 0.005), having a low income (p = 0.030), being employed (p = 0.008), having missed diabetes education in the last year (p = 0.002), and lower self-care confidence (p < 0.0001). Lower self-care confidence was associated with having diabetes for < 10 years (p = 0.008), and having at least one comorbid condition (p = 0.006). Conclusions Determinants of self-care maintenance, monitoring, management and confidence include both clinical and socio-demographic variables. Modifiable determinants such as self-care confidence and diabetes self-care management education could be used to tailor interventions to improve diabetes self-care

The adaptor protein Rai/ShcC promotes astrocyte-dependent inflammation during experimental autoimmune encephalomyelitis

Th17 cells have been casually associated to the pathogenesis of autoimmune disease. We have previously demonstrated that Rai/ ShcC, a member of the Shc family of adaptor proteins, negatively regulates Th17 cell differentiation and lupus autoimmunity. In this study, we have investigated the pathogenic outcome of the Th17 bias associated with Rai deficiency on multiple sclerosis development, using the experimental autoimmune encephalomyelitis (EAE) mouse model.We found that, unexpectedly, EAE was less severe in Rai2/2 mice compared with their wild-type counterparts despite an enhanced generation of myelin-specific Th17 cells that infiltrated into the CNS. Nevertheless, when adoptively transferred into immunodeficient Rai+/+ mice, these cells promoted a more severe disease compared with wild-type encephalitogenic Th17 cells. This paradoxical phenotype was caused by a dampened inflammatory response of astrocytes, which were found to express Rai, to IL-17. The results provide evidence that Rai plays opposite roles in Th17 cell differentiation and astrocyte activation, with the latter dominant over the former in EAE, highlighting this adaptor as a potential novel target for the therapy of multiple sclerosis

Rapid HIA to support decision making in the Public Administration in Italy THE Vispa PROJECT

Since a decade HIA background and practice is growing up in Italy. The Ministry of Health endorsed the promotion and development of HIA practice funding the VISPA project to adapt HIA processes and tools in Public Administration (PA) activities and to prepare recommendations in view of national guideline. Methods/approaches. The feasibility of a rapid HIA protocol for plans and projects embedded in the PA decision-making process was tested involving 34 trained operators in six different Italian Regions. Twenty-eight casestudies regarding waste, city planning, energy, industrial districts and farms, were selected by a screening-scoping exercise. The developed toolkit supported the involved Public Officials during the phases of assessment, appraisal and reporting of results. Results. The proposed rapid HIA was always feasible with few exceptions. Positive outputs were achieved in terms of capacity building, identification of relevant subject, integration with other assessment tools. A final step-by-step procedure was validated and actors, tools and timing were identified. An audio-video guide was released to facilitate the use and transferability of the products. Conclusions. The experimental approach adopted highlighted a positive feedback. The burdensome of the application was recognised and critical issues appeared the citizen participation and the inter-departments cooperation