Docosahexaenoic acid (DHA) promotes immunogenic apoptosis in human multiple myeloma cells, induces autophagy and inhibits STAT3 in both tumor and dendritic cells

Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid found in fish oil, is a multi-target agent and exerts anti-inflammatory and anticancer activities alone or in combination with chemotherapies. Combinatorial anticancer therapies, which induce immunogenic apoptosis, autophagy and STAT3 inhibition have been proposed for long-term therapeutic success. Here, we found that DHA promoted immunogenic apoptosis in multiple myeloma (MM) cells, with no toxicity on PBMCs and DCs. Immunogenic apoptosis was shown by the emission of specific DAMPs (CRT, HSP90, HMGB1) by apoptotic MM cells and the activation of their pro-apoptotic autophagy. Moreover, immunogenic apoptosis was directly shown by the activation of DCs by DHA-induced apoptotic MM cells. Furthermore, we provided the first evidence that DHA activated autophagy in PBMCs and DCs, thus potentially acting as immune stimulator and enhancing processing and presentation of tumor antigens by DCs. Finally, we found that DHA inhibited STAT3 in MM cells. STAT3 pathway, essential for MM survival, contributed to cancer cell apoptosis by DHA. We also found that DHA inhibited STAT3 in blood immune cells and counteracted STAT3 activation by tumor cell-released factors in PBMCs and DCs, suggesting the potential enhancement of the anti-tumor function of multiple immune cells and, in particular, that of DCs

Extraction socket preservation using porcine-derived collagen membrane alone or associated with porcine-derived bone. Clinical results of randomized controlled study

The aim of present randomized controlled clinical trial was to clinically evaluate hard tissue changes after extraction socket preservation procedures compared to natural spontaneous healing

News narratives about migrants 'at the border' in Italian and Spanish online news media, 2013-2015

This thesis investigates the representation of African migrants in Italian and Spanish online news media through the lens of the border. By employing an interdisciplinary approach, in which the migrant crossings of the Libya-Italy and Morocco-Spain borders are a central research focus, this work explores the written and visual representations of migrants from September 2013 to August 2015. Throughout this time frame, which represents a crucial period in the long-lasting story of migration from Africa towards Europe, the analysis of online news items demonstrates that news media representations of migrants depend on the very nature of the borders that migrants attempt to cross while paralleling the institutional standpoints provided by official news sources. Furthermore, from a cultural perspective, the research here explores the features of online news narratives as well as the role of the working practices of Italian and Spanish journalists in the production of migrant representations. It also discusses the meanings that are embedded in such news narratives. As a result, through an innovative methodological approach, which includes the analysis of online news items and interviews with journalists, this thesis provides a critical framework for the investigation of online news production and contemporary journalism more broadly

Bone healing in extraction sockets covered with collagen membrane alone or associated with porcine-derived bone graft: a comparative histological and histomorphometric analysis

The present paper reports data of a randomized study aimed to analyse and compare the histologic and histomorphometric aspects of bone healing in extraction sites covered with collagen membrane alone or associated with porcine-derived bone graft

Cerebral gray matter volume in patients with chronic migraine: correlations with clinical features

Abstract Background To date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM. Methods Twenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients’ clinical features and GM maps were regressed. Results Initially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month. Conclusion No gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage

Dynamic spectral signatures of mirror movements in the sensorimotor functional connectivity network of patients with Kallmann syndrome

In Kallmann syndrome (KS), the peculiar phenomenon of bimanual synkinesis or mirror movement (MM) has been associated with a spectral shift, from lower to higher frequencies, of the resting-state fMRI signal of the large-scale sensorimotor brain network (SMN). To possibly determine whether a similar frequency specificity exists across different functional connectivity SMN states, and to capture spontaneous transitions between them, we investigated the dynamic spectral changes of the SMN functional connectivity in KS patients with and without MM symptom. Brain MRI data were acquired at 3 Tesla in 39 KS patients (32 without MM, KSMM-, seven with MM, KSMM+) and 26 age- and sex-matched healthy control (HC) individuals. The imaging protocol included 20-min rs-fMRI scans enabling detailed spectro-temporal analyses of large-scale functional connectivity brain networks. Group independent component analysis was used to extract the SMN. A sliding window approach was used to extract the dynamic spectral power of the SMN functional connectivity within the canonical physiological frequency range of slow rs-fMRI signal fluctuations (0.01-0.25 Hz). K-means clustering was used to determine (and count) the most recurrent dynamic states of the SMN and detect the number of transitions between them. Two most recurrent states were identified, for which the spectral power peaked at a relatively lower (state 1) and higher (state 2) frequency. Compared to KS patients without MM and HC subjects, the SMN of KS patients with MM displayed significantly larger spectral power changes in the slow 3 canonical sub-band (0.073-0.198 Hz) and significantly fewer transitions between state 1 (less recurrent) and state 2 (more recurrent). These findings demonstrate that the presence of MM in KS patients is associated with reduced spontaneous transitions of the SMN between dynamic functional connectivity states and a higher recurrence and an increased spectral power change of the high-frequency state. These results provide novel information about the large-scale brain functional dynamics that could help to understand the pathologic mechanisms of bimanual synkinesis in KS syndrome and, potentially, other neurological disorders where MM may also occur

Increased neural connectivity between the hypothalamus and cortical resting-state functional networks in chronic migraine

Objective The findings of resting-state functional MRI studies have suggested that abnormal functional integration between interconnected cortical networks characterises the brain of patients with migraine. The aim of this study was to investigate the functional connectivity between the hypothalamus, brainstem, considered as the migraine generator, and the following areas/networks that are reportedly involved in the pathophysiology of migraine: default mode network (DMN), executive control network, dorsal attention system, and primary and dorsoventral visual networks. Methods Twenty patients with chronic migraine (CM) without medication overuse and 20 healthy controls (HCs) were prospectively recruited. All study participants underwent 3-T MRI scans using a 7.5-min resting-state protocol. Using a seed-based approach, we performed a ROI-to-ROI analysis selecting the hypothalamus as the seed. Results Compared to HCs, patients with CM showed significantly increased neural connectivity between the hypothalamus and brain areas belonging to the DMN and dorsal visual network. We did not detect any connectivity abnormalities between the hypothalamus and the brainstem. The correlation analysis showed that the severity of the migraine headache was positively correlated with the connectivity strength of the hypothalamus and negatively with the connectivity strength of the medial prefrontal cortex, which belongs to the DMN. Conclusion These data provide evidence for hypothalamic involvement in large-scale reorganisation at the functional-network level in CM and in proportion with the perceived severity of the migraine pain

Sparsely-connected autoencoder (SCA) for single cell RNAseq data mining

Abstract Single-cell RNA sequencing (scRNAseq) is an essential tool to investigate cellular heterogeneity. Thus, it would be of great interest being able to disclose biological information belonging to cell subpopulations, which can be defined by clustering analysis of scRNAseq data. In this manuscript, we report a tool that we developed for the functional mining of single cell clusters based on Sparsely-Connected Autoencoder (SCA). This tool allows uncovering hidden features associated with scRNAseq data. We implemented two new metrics, QCC (Quality Control of Cluster) and QCM (Quality Control of Model), which allow quantifying the ability of SCA to reconstruct valuable cell clusters and to evaluate the quality of the neural network achievements, respectively. Our data indicate that SCA encoded space, derived by different experimentally validated data (TF targets, miRNA targets, Kinase targets, and cancer-related immune signatures), can be used to grasp single cell cluster-specific functional features. In our implementation, SCA efficacy comes from its ability to reconstruct only specific clusters, thus indicating only those clusters where the SCA encoding space is a key element for cells aggregation. SCA analysis is implemented as module in rCASC framework and it is supported by a GUI to simplify it usage for biologists and medical personnel

Adherence to Mediterranean Diet and Its Association with Maternal and Newborn Outcomes

Background: Pregnancy is a crucial stage in a woman’s life and can be affected by epigenetic and environmental factors. Diet also plays a key role in gestation. This study aimed to evaluate how a greater or lesser adherence to the Mediterranean Diet (MD) influences specific parameters of mother and newborn. Methods: After delivery, the women participating in the study answered a questionnaire: demographic information; anthropometric data (pre-pregnancy weight, height, and gestational weight gain); dietary habits information (adherence to MD before and during pregnancy, using the validated Mediterranean Diet Adherence Screener (MEDAS), quality of protein intake); pregnancy information (onset of complications, cesarean/vaginal delivery, gestational age at birth, birth weight, birth length); and clinical practitioner for personalized dietary patterns during pregnancy. Results: A total of 501 respondents have been included in the study, and 135 were excluded for complications. Women who followed the advice of clinical nutritionists showed better adherence to MD (p = 0.02), and the baby’s birth weight was higher (p = 0.02). Significant differences in gestational weight gain (p < 0.01) between groups with dissimilar diet adherence were demonstrated. Conclusion: Our data demonstrate a significant relationship between adherence to MD and birthweight

Neisseria meningitidis Factor H Binding Protein Surface Exposure on Salmonella Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases

GMMA, outer membrane vesicles resulting from hyperblebbing mutated bacterial strains, are a versatile vaccine platform for displaying both homologous and heterologous antigens. Periplasmic expression is a popular technique for protein expression in the lumen of the blebs. However, the ability of internalized antigens to induce antibody responses has not been extensively investigated. Herein, the Neisseria meningitidis factor H binding protein (fHbp) was heterologously expressed in the lumen of O-antigen positive (OAg+) and O-antigen negative (OAg-) Salmonella Typhimurium GMMA. Only the OAg- GMMA induced an anti-fHbp IgG response in mice if formulated on Alum, although it was weak and much lower compared to the recombinant fHbp. The OAg- GMMA on Alum showed partial instability, with possible exposure of fHbp to the immune system. When we chemically conjugated fHbp to the surface of both OAg+ and OAg- GMMA, these constructs induced a stronger functional response compared to the fHbp immunization alone. Moreover, the OAg+ GMMA construct elicited a strong response against both the target antigens (fHbp and OAg), with no immune interference observed. This result suggests that antigen localization on GMMA surface can play a critical role in the induction of an effective immune response and can encourage the development of GMMA based vaccines delivering key protective antigens on their surface