Fibronectin Extra Domains tune cellular responses and confer topographically distinct features to fibril networks

International audienceCellular fibronectin (FN; also known as FN1) variants harboring one or two alternatively spliced so-called extra domains (EDB and EDA) play a central bioregulatory role during development, repair processes and fibrosis. Yet, how the extra domains impact fibrillar assembly and function of the molecule remains unclear. Leveraging a unique biological toolset and image analysis pipeline for direct comparison of the variants, we demonstrate that the presence of one or both extra domains impacts FN assembly, function and physical properties of the matrix. When presented to FN-null fibroblasts, extra domain-containing variants differentially regulate pH homeostasis, survival, and TGF- β by tuning the magnitude of cellular responses, rather than triggering independent molecular switches. Numerical analyses of fiber topologies highlight significant differences in variant-specific structural features and provide a first step for the development of a generative model of FN networks to unravel assembly mechanisms and investigate the physical and functional versatility of extracellular matrix landscapes

Improvement of bone physiology and life quality due to association of risedronate and anastrozole

The endocrine therapy is the new frontiers of many breast cancers hormone sensitive. Hormone therapy for treating women with hormone receptor-positive cancer suppresses breast cancer growth either by reducing estrogen synthesis or by interfering with the action of estrogen within tumor cells. In this prospective randomized observational study we investigate the effect of adjuvant anastrozole in monotherapy or associated with risedronate on bone physiology and quality of life in postmenopausal, hormone-sensitive early breast cancer women at mild to moderate risk of fragility fractures. Methods: 84 women were randomly assigned to receive anastrozole alone (group A) or anastrozole plus oral risedronate (group A+R). At baseline and after 24 months lumbar spine (LS) and femoral neck (FN) BMD were evaluated with dual-energy x-ray absorptiometry and health-related quality of life (HRQoL) was examined using the short-form healthy survey. Results: After 24 months, the group A+R has showed a significant increase in T-score for LS (p < 0.05) and for FN (p < 0.05) whereas women of group A had a statistically significant rate of bone loss both in LS T-score (p < 0.05) and in FN (p < 0.05). A significant change in T-score BMD was seen for group A+R compared with group A at the LS (p = 0.04) and at FN (p = 0.04). Finally, group A+R showed an overall significant improvement of health profile (SF-36) in group A (p = 0.03). Conclusion: Postmenopausal breast cancer women with osteopenia during treatment with anastrozole have considerable risk of developing osteoporosis during the first 2 years; preventive measures such as healthy lifestyle and daily supplements of calcium and vitamin D alone seem to be insufficient in holding their bones healthy. Our findings suggest the usefulness of addition of risedronate in order to prevent aromatase inhibitors- related bone loss, not only in case of high-risk of fractures, but also for women at mild-moderate risk. This determines a significant improvement in bone health and a positive impact on HRQoL

The Rorschach Test Evaluation in Chronic Childhood Migraine: A Preliminary Multicenter Case–Control Study

ObjectAbout 1.2–3.2% of children at 7 years of age with increasing age up to 4–19% in adolescents are suffering from migraine without aura (MwA). The aim of the present study is investigating the personality style associated with children and adolescents affected by MwA, administrating the Rorschach test, and comparing with typical developing healthy controls (TD).Methods137 patients (74 males), aged 7.3–17.4 years (mean age 11.4, SD 3.02 years), affected by MwA according to the IHs-3 criteria. The Rorschach variables were treated as numerical variables and statistically tested with t-Student’s analysis.ResultsNo statistical differences were found between the MwA and TD for age (p = 0.55), and gender (p = 0.804). From the comparison between the two samples, MwA group shows lower W responses (p < 0.001), good quality W responses (p < 0.001), high frequency of detailed responses (p < 0.001), the presence of even minor form of good quality responses (p < 0.001), increased presence of animals answers (A%) (p < 0.001), more frequent trivial answers (Ban%) (p < 0.001).DiscussionRorschach interpretation pinpointed many interesting and, perhaps, peculiar aspects in our MwA population such as a trend predisposition for: analytical reasoning rather than synthetic, ease/practicality rather than creativity, oppositionality rather than external adaptation to the environment that may be interpreted as effect of general maladaptivity

Eribulin for metastatic breast cancer (MBC) treatment: a retrospective, multicenter study based in Campania, south Italy (Eri-001 trial)

Background On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease.Methods In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC.Results Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3-4 toxicities were neutropaenia and neurotoxicity.Conclusions With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC

Eribulin for metastatic breast cancer (MBC) treatment. A retrospective, multicenter study based in Campania, South Italy (ERI-001 trial)

Background On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease.Methods In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC.Results Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3-4 toxicities were neutropaenia and neurotoxicity.Conclusions With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC

Maternal Stress and Coping Strategies in Developmental Dyslexia: An Italian Multicenter Study

BackgroundStudies about the impact of developmental dyslexia (DD) on parenting are scarce. Our investigation aimed to assess maternal stress levels and mothers’ copying styles in a population of dyslexic children.MethodsA total of 874 children (500 boys, 374 girls; mean age 8.32 ± 2.33 years) affected by DD was included in the study. A total of 1,421 typically developing children (789 boys, 632 girls; mean age 8.25 ± 3.19 years) were recruited from local schools of participating Italian Regions (Abruzzo, Calabria, Campania, Puglia, Umbria, Sicily) and used as control-children group. All mothers (of both DD and typically developing children) filled out an evaluation for parental stress (Parenting Stress Index—Short Form) and coping strategies [Coping Inventory for Stressful Situations (CISS)].ResultsNo statistical differences for mean age (p = 0.456) and gender (p = 0.577) were found between DD and control children. Mothers of children affected by DD showed an higher rate of all parental stress indexes (Parental Distress domain p < 0.001, Difficult Child p < 0.001, Parent–Child Dysfunctional Interaction p < 0.001, and Total Stress subscale score p < 0.001) than controls mothers. According to the CISS evaluation, mothers of DD children reported a significantly higher rate of emotion-oriented (p < 0.001) and avoidance-oriented (p < 0.001) coping styles than mothers of typical developing children. On the other hand, a lower representation of task-oriented coping style was found in mothers of DD children (p < 0.001) in comparison to mothers of control-children.ConclusionOur study shows the clinical relevance of the burden carried by the mothers of children affected by DD and suggests the importance to assess parents, particularly mothers, to improve family compliance and clinical management of this disorder