The development of number processing and its relation to other parietal functions in early childhood

The project has explored the developmental trajectories of several cognitive functions related to different brain regions: parietal cortex (quantity manipulation, finger gnosis, visuo-spatial memory and grasping abilities) and occipito-temporal cortex (face and object processing), in order to investigate their contributions to the acquisition of formal arithmetic in the first year of schooling. We tested preschooler, first grader and adult subjects, using correlational cross-sectional and longitudinal approaches. Results show that anatomical proximity is a strong predictor of behavioural correlations and of segregation between dorsal and ventral streams’ functions. This observation is particularly prominent in children: within parietal functions, there is a progressive separation across functions during development. During preschool age, presymbolic and symbolic number systems follow distinct developmental trajectories that converge during the first year of primary school. Indeed a possible cause of this phenomenon could be due to the refinement of the numerosity acuity during the acquisition of symbolic knowledge for numbers. Among the tested parietal functions, we observe a strong association between the numerical and the finger domain, especially in children. In preschoolers, finger gnosis is strongly associated with non-symbolic quantity processing, while in first graders it links up to symbolic mental arithmetic. This finding may reflect a pre-existing anatomical connection between the cortical regions supporting the quantity and finger-related functions in early childhood. In contrast, first graders exhibit a finger-arithmetic association more influenced by functional factors and cultural-based strategies (e.g. finger counting). Longitudinal data has allowed us to individuate which cognitive functions measured in kindergarteners predicts better the success in mental arithmetic in the first year of school. Results show that finger gnosis, as well as quantity and space–related abilities all concur at shaping the success in mental calculation in first graders. These results are important because, primarily, they are the first to observe a strong relation between visuo-spatial, finger and quantity related abilities in young children, and, secondly, because the longitudinal design provides strong evidence for a causal link between these functions and the success in formal arithmetic. These results suggest that educational programs should include training in each of these cognitive domains in mathematic classes. Finally, specific applications of these findings can be found within the domain of educational neuroscience and for the rehabilitation of children with numerical deficits (dyscalculia)

a teleoperation system for micro invasive brain surgery

AbstractThis paper deals with controller design issues for a neurosurgical teleoperator system. The specific application of interest consists of remotely inserting a linear-stage rigid endoscope into the patient's brain for microinvasive neurosurgery interventions. This work aims at evaluating advantages and drawbacks of using a general-purpose control architecture versus a simpler task-oriented architecture, from a point of view of stability and transparency. Experiments revealed that in spite of its simplicity, the task-oriented design allows an improvement in the trade-off between performance, transparency and stability requirements

Subcutaneous panniculitis-like T-cell lymphoma presenting with diffuse cutaneous edema in a 2-year-old child

N/

facial emotion recognition performance influences executive control impairment in anorexia nervosa an exploratory study

AbstractObjectivesSince evidence on executive control among women with Anorexia or Bulimia Nervosa (AN/BN) are somehow inconclusive, we aimed to explore whether performance in set-shifting in AN/BN might be influenced by Facial Emotion Recognition (FER).MethodsWe randomly recruited women with a diagnosis of AN or BN, from an Eating Disorders Outpatient Clinic in Italy, as well as healthy controls (HCs). We evaluated with established tools: diagnosis (Eating Disorder Examination- EDE-17.0), executive control (Intra-Extra Dimensional Set Shift-IED) and FER (Ekman 60 Faces Test-EK-60F). Univariate distributions by diagnostic subgroups were assessed on sociodemographic and clinical variables, which were selected for subsequent multiple linear regression analyses.ResultsWomen with AN performed significantly worse than HCs on IED adjusted total errors. HCs scored significantly better than AN and BN on EK-60F fear subscale. Although IED set shifting was associated (p = 0.008) with AN, after controlling for age, EK-60F fear subscale, alexithymia and depression (i.e., clinically relevant covariates identified a priori from the literature, or associated with AN/BN at univariate level), this association could not be confirmed.ConclusionsImpaired executive control may not be a distinctive feature in women with AN, since several clinical characteristics, including fear recognition ability, are likely to have an important role. This has significant implications for relevant interventions in AN, which should aim at also improving socio-emotional processing

ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation

Adenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (CECR1) gene, currently named ADA2. The disease has a wide clinical spectrum encompassing early-onset vasculopathy (targeting skin, gut and central nervous system), recurrent fever, immunodeficiency and bone marrow dysfunction. Different therapeutic options have been proposed in literature, but only steroids and anti-cytokine monoclonal antibodies (such as tumor necrosis factor inhibitor) proved to be effective. If a suitable donor is available, hematopoietic stem cell transplantation (HSCT) could be curative. Here we describe a case of ADA2 deficiency in a 4-year-old Caucasian girl. The patient was initially classified as autoimmune neutropenia and then she evolved toward an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. The diagnosis of ALPS became uncertain due to atypical clinical features and normal FAS-induced apoptosis test. She was treated with G-CSF first and subsequently with immunosuppressive drugs without improvement. Only HSCT from a 9/10 HLA-matched unrelated donor, following myeloablative conditioning, completely solved the clinical signs related to ADA2 deficiency. Early diagnosis in cases presenting with hematological manifestations, rather than classical vasculopathy, allows the patients to promptly undergo HSCT and avoid more severe evolution. Finally, in similar cases highly suspicious for genetic disease, it is desirable to obtain molecular diagnosis before performing HSCT, since it can influence the transplant procedure. However, if HSCT has to be performed without delay for clinical indication, related donors should be excluded to avoid the risk of relapse or partial benefit due to a hereditary genetic defect

Paediatric recurrent pericarditis: Appropriateness of the standard of care and response to IL1-blockade

Objective: To analyse, in a cohort of paediatric patients with recurrent pericarditis (RP) undergoing anti-IL-1 treatment: the agent and dosing used as first line treatment, the long-term efficacy of IL1-blockers, the percentage of patients achieving a drug-free remission, the presence of variables associated with drug-free remission. Study design: Data were collected from patients' charts. Annualized relapse rate (ARR) was used for evaluation of treatment efficacy, bivariate logistic regression analysis for variables associated with drug-free remisison. Results: 58 patients, treated between 2008 and 2018, were included in the study (mean follow-up 2.6 years). 14/56 patients non-responsive to first line drugs were under-dosed. 57 patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (p<0.0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (p<.0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (p=0.215). At last follow-up only 9/58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. Conclusion: This study shows that most of the pediatric patients with RP needing IL-1 blockade received an inadequate treatment with first line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug free-remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL1α in the pathogenesis of RP

ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation

Adenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (CECR1) gene, currently named ADA2. The disease has a wide clinical spectrum encompassing early-onset vasculopathy (targeting skin, gut and central nervous system), recurrent fever, immunodeficiency and bone marrow dysfunction. Different therapeutic options have been proposed in literature, but only steroids and anti-cytokine monoclonal antibodies (such as tumor necrosis factor inhibitor) proved to be effective. If a suitable donor is available, hematopoietic stem cell transplantation (HSCT) could be curative. Here we describe a case of ADA2 deficiency in a 4-year-old Caucasian girl. The patient was initially classified as autoimmune neutropenia and then she evolved toward an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. The diagnosis of ALPS became uncertain due to atypical clinical features and normal FAS-induced apoptosis test. She was treated with G-CSF first and subsequently with immunosuppressive drugs without improvement. Only HSCT from a 9/10 HLA-matched unrelated donor, following myeloablative conditioning, completely solved the clinical signs related to ADA2 deficiency. Early diagnosis in cases presenting with hematological manifestations, rather than classical vasculopathy, allows the patients to promptly undergo HSCT and avoid more severe evolution. Finally, in similar cases highly suspicious for genetic disease, it is desirable to obtain molecular diagnosis before performing HSCT, since it can influence the transplant procedure. However, if HSCT has to be performed without delay for clinical indication, related donors should be excluded to avoid the risk of relapse or partial benefit due to a hereditary genetic defect

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Background: Activated phosphoinositide-3-kinase d syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain of-function (GOF) disease; and identify predictors of severity in APDS. Methods: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. Results: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. Conclusions: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients. (J Allergy Clin Immunol 2023;152:984-96.

VENETISM: BETWEEN HISTORICAL REVISIONISM AND AUTONOMOUS MOVEMENTS

non

A pneumonia that does not improve

N/