Although the relationship between developmental dyslexia (DD) and the risk of occurrence of internalizing symptomatology has been widely investigated in the extant literature, different findings have ...been reported. In this study, two experiments with two general purposes are presented. The first study investigates whether the differences in the severity of internalizing symptoms between DD and controls are greater in students attending secondary school than in those attending primary school. Sixty-five DD and 169 controls attending primary and secondary school took part in the first study. The diagnosis of dyslexia was obtained from standardized reading tests; internalizing symptom severity was assessed with the Self Administrated Psychiatric Scales for Children and Adolescents questionnaire. The results showed that adolescents with dyslexia had an increased level of self-perceived anxiety, depression and somatic symptoms, whereas no significant differences between DD and controls emerged in childhood. In the second study, a cohort of adolescents attending secondary school (DD = 44; controls = 51) was closely analyzed to clarify whether contextual and subjective factors could contribute toward exacerbating the risk of internalizing symptomatology at that age. Internalizing symptom severity was assessed with the Child Behavior Checklist, Youth Self Report questionnaire, decision-making factors were measured with the Melbourne Decision Making Questionnaire, and student's quality of life was gaged using the Clipper test. The results showed that high levels of internalizing symptoms in DD were associated with a low level of self-esteem and the tendency to react to problematic situations with hyperactivation. By contrast, positive relationships with peers were associated with low symptom severity. In conclusion, the intensified internalizing symptoms that could emerge in adolescents in association with the presence of dyslexia are predicted by social protective and risk factors that are associated with symptom severity. Accordingly, the results suggest that remediation programs for dyslexia should include implementing motivation strategies, self-esteem enhancement activities and building peers networks that, starting in childhood, can prevent the appearance of internalizing symptoms.
•Visual perception development is associated with cognitive development.•Motion perception and form discrimination develop untill adolescence.•Motion and form coherence test norms allow the ...recognition of atypical developmental trajectories.
Literature on the development of global motion and global form perception demonstrated their asynchronous developmental trajectories. However, former studies have failed to clearly establish the critical period of maturation for these specific abilities. This study aimed to analyze the developmental trajectories of global motion and global form discrimination abilities by controlling for basic visual functions and general cognitive ability and to present the global motion and global form normative scores. A sample of 456 children and adolescents (4–17 years of age) and 76 adults recruited from the Italian and Swedish general population participated in the study. Motion and form perception were evaluated by the motion coherence test and form coherence test, respectively. Raven’s matrices were used to assess general cognitive ability, the Lea Hyvärinen chart test was used for full- and low-contrast visual acuity, and the TNO test was used for stereopsis. General cognitive ability and basic visual functions were strongly related to motion and form perception development. Global motion perception had an accelerated maturation compared with global form perception. For motion perception, an analysis of the oblique effect’s development showed that it is present at 4 years of age. The standardized scores of global motion and form coherence tests can be used for clinical purposes.
Behavioral Inhibition (BI) is a temperamental trait characterized by fear and wariness in reaction to new and unfamiliar stimuli, both social and non-social. BI has been recognized as possible ...forerunner of anxiety disorders, especially social anxiety and phobia; therefore, its assessment is clinically relevant. The present study aimed to examine the psychometric properties of the Italian adaptation of the Behavioral Inhibition Questionnaire (BIQ), which measures BI in preschool children. The BIQ was completed by 417 Italian parents (230 mothers, 187 fathers) of 270 preschoolers aged 3–5. Confirmatory factor analysis showed a good internal validity: the factorial structure was corresponding to the original six-factor version. Results showed excellent internal consistency, significant item-total correlations, good inter-rater reliability, convergent validity (by correlating the BIQ with the Italian Questionnaires of Temperament-QUIT, the Anxiety-Shy Conner’s Scale and the Laboratory Temperament Assessment Battery) and discriminant validity (i.e., no correlation with Conners’ ADHD scale). Significant correlations emerged between BI indexes and total BIQ scores of parents and maternal (but not paternal) versions of the questionnaire. Altogether, the results are promising and consistent with previous validation studies, suggesting the BIQ as a reliable and valid measure for evaluating parents’ perception of BI in Italian preschoolers.
Nested stromal-epithelial tumor(NSET) is a nonhepatocytic and non-biliary tumor of the liver consisting of nests of epithelial and spindled cells with associated myofibroblastic stroma and variable ...intra-lesional calcification and ossification, which represents a very rare and challenging disease. Most of the reported cases have been treated with surgery, obtaining a long survival outcome. Here, we report the case of a 31-year-old Caucasian man who underwent surgery at our institution for a large, lobulated, multinodular mass of the right hemi-liver. The histological exam confirmed the diagnosis of NSET. After 6 mo from surgery, a liver recurrence was described and a chemoembolization was performed. After a further disease progression, based on the correlation between the histological features of the disease and those of the hepatoblastoma, a similar chemotherapy regimen(with cisplatin and ifosfamide/mesna chemotherapy, omitting doxorubicin due to liver impairment) was administered. However, infection of the biliary catheter required a dose modification of the treatment. No benefit was noted and a progression of disease was radiologically assessed after only four cycles. The worsening of the clinical status prevented further treatments, and the patient died a few months later. This case report documents how the NSET might have an aggressive and non-preventable behavior. No chemotherapy schedules with a proved efficacy are available, and new data are needed to shed light on this rare neoplasm.
Introduction
The microsatellite-instable gastric cancer subtype, because of its supposed high antigenic potential, is a promising candidate for immunotherapy. We analyzed if the presence of a ...defective mismatch repair (MMR) system is associated with other markers of immune response and their relationship with outcome in advanced gastric cancer patients.
Methods
We analyzed the relationship between clinical outcome and MMR status, the presence of tumor-infiltrating lymphocytes (TIL), lymphocytosis, and neutrophil-to-lymphocyte ratio (NLR) in metastatic gastric cancer patients treated with a chemotherapy doublet in the first-line setting. Other stratification factors were sex, age, Eastern Cooperative Oncology Group performance status, adjuvant/neoadjuvant chemotherapy, metastatic sites, and histotype.
Results
One hundred three patients were eligible for analysis. Defective MMR was found in 15 patients (14 %), TILs were found in 18 patients (17 %), lymphocytosis was found in 24 patients (23 %), and high NLR was found in 75 patients (72 %). Significant correlations were found between defective MMR and TIL positivity (
p
= 0.0004), between defective MMR and lymphocytosis (
p
= 0.0062), between defective MMR and low NLR (
p
= 0.000069), and between TIL positivity and lymphocytosis (
p
= 0.000147). All factors had a statistically significant impact on overall survival, although on multivariate analysis only defective MMR (
p
= 0.0001) and TIL positivity (
p
= 0.0192) maintained their independent prognostic role. Similar results were observed for progression-free survival, with defective MMR (
p
= 0.0001) and TIL positivity (
p
= 0.0195) maintaining their prognostic role on multivariate analysis.
Conclusions
Our analysis confirms the favorable prognosis of metastatic gastric cancer patients with a defective MMR system and suggests that expression of TILs might also be linked to better outcome. Because of the correlation between defective MMR status and measures of immune system activity, this group of patients would be the best candidates for novel immunotherapy-based therapies.
Although new treatment modalities changed the global approach to hepatocellular carcinoma (HCC), this disease still represents a medical challenge. Currently, the therapeutic stronghold is sorafenib, ...a tyrosine kinase inhibitor (TKI) directed against the vascular endothelial growth factor (VEGF) family. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and thus tumour growth control. The aim of our study was to evaluate the role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. From a multicentre experience 148 samples (tumour or blood samples) of HCC patients receiving sorafenib were tested for VEGF‐A, VEGF‐C and VEGFR‐1,2,3 single nucleotide polymorphisms (SNPs). Patients' progression‐free survival (PFS) and overall survival (OS) were analysed. At univariate analysis VEGF‐A alleles C of rs25648, T of rs833061, C of rs699947, C of rs2010963, VEGF‐C alleles T of rs4604006, G of rs664393, VEGFR‐2 alleles C of rs2071559, C of rs2305948 were significant predictors of PFS and OS. At multivariate analysis rs2010963, rs4604006 and BCLC (Barcelona Clinic Liver Cancer) stage resulted to be independent factors influencing PFS and OS. Once prospectively validated, the analysis of VEGF and VEGFR SNPs may represent a clinical tool to better identify HCC patients more likely to benefit from sorafenib. On the other hand, the availability of more accurate predictive factors could help avoiding unnecessary toxicities to potentially resistant patients who may be optimal candidates for different treatments interfering with other tumour molecular pathways.
What's new?
The tyrosine kinase inhibitor sorafenib, which is directed against vascular endothelial growth factor (VEGF), is considered to be the standard of treatment for hepatocellular carcinoma (HCC). Nevertheless, some tumors fail to respond to the drug, possibly owing to variations in the VEGF gene. Here, investigation of single nucleotide polymorphisms (SNPs) in VEGF and VEGFR in HCC patients who received sorafenib reveals that certain SNPs are significant predictors of progression free survival and overall survival. The identified SNPs may represent valuable assets in the identification of HCC patients who are likely to benefit from sorafenib treatment.
Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative ...damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE.
Minipumps allowing continuous intracerebroventricular (icv) infusion of siponimod for 4 weeks were implanted into C57BL/6 mice subjected to MOG35-55-induced EAE. Electrophysiology, immunohistochemistry, western blot, qPCR experiments, and peripheral lymphocyte counts were performed. In addition, the effect of siponimod on activated microglia was assessed in vitro to confirm the direct effect of the drug on CNS-resident immune cells.
Siponimod administration (0.45 μg/day) induced a significant beneficial effect on EAE clinical scores with minimal effect on peripheral lymphocyte counts. Siponimod rescued defective GABAergic transmission in the striatum of EAE, without correcting the EAE-induced alterations of glutamatergic transmission. We observed a significant attenuation of astrogliosis and microgliosis together with reduced lymphocyte infiltration in the striatum of EAE mice treated with siponimod. Interestingly, siponimod reduced the release of IL-6 and RANTES from activated microglial cells in vitro, which might explain the reduced lymphocyte infiltration. Furthermore, the loss of parvalbumin-positive (PV+) GABAergic interneurons typical of EAE brains was rescued by siponimod treatment, providing a plausible explanation of the selective effects of this drug on inhibitory synaptic transmission.
Altogether, our results show that siponimod has neuroprotective effects in the CNS of EAE mice, which are likely independent of its peripheral immune effect, suggesting that this drug could be effective in limiting neurodegenerative pathological processes in MS.
Multiple sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by inflammation-driven synaptic abnormalities. Interleukin-9 (IL-9) is emerging as a ...pleiotropic cytokine involved in MS pathophysiology.
Through biochemical, immunohistochemical, and electrophysiological experiments, we investigated the effects of both peripheral and central administration of IL-9 on C57/BL6 female mice with experimental autoimmune encephalomyelitis (EAE), a model of MS.
We demonstrated that both systemic and local administration of IL-9 significantly improved clinical disability, reduced neuroinflammation, and mitigated synaptic damage in EAE. The results unveil an unrecognized central effect of IL-9 against microglia- and TNF-mediated neuronal excitotoxicity. Two main mechanisms emerged: first, IL-9 modulated microglial inflammatory activity by enhancing the expression of the triggering receptor expressed on myeloid cells-2 (TREM2) and reducing TNF release. Second, IL-9 suppressed neuronal TNF signaling, thereby blocking its synaptotoxic effects.
The data presented in this work highlight IL-9 as a critical neuroprotective molecule capable of interfering with inflammatory synaptopathy in EAE. These findings open new avenues for treatments targeting the neurodegenerative damage associated with MS, as well as other inflammatory and neurodegenerative disorders of the central nervous system.
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