The museum complex of Pitti Palace is one of the strategic projects of UNESCO Management Plan, called The prince's path, together with Uffizi Gallery, Vasari Corridor and Boboli Gardens, constituting ...the site that, perhaps not surprisingly, in 2014 the Ministry equipped with managerial, administrative-economic autonomy. If the post-war history of the Palace has been characterized by inadequate investments of resources and tools, also for the purposes of knowledge of the architectural heritage (the first studies of that period, remain the main bibliographic references to this day) and of the relative maintenance, the so-called 'Franceschini Reform' has inaugurated a new season for the Site, in which the administration has the opportunity to deepen and experiment strategies and actions aimed at the practice of programmed conservation. As regards the monumental complex of Pitti Palace, the contribution presents interventions, analyzes and programs which have been conceived and conducted with a methodological approach that places analysis and monitoring of the state of conservation of the heritage.
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, ...studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
Pituitary gland volume (PGV) increases during childhood and adolescence in a sex-specific manner, and previous research suggests that puberty may be associated with PGV development. However, existing ...research to date has focused on sex hormones associated with gonadarche. Given the role of the pituitary gland in hypothalamic-pituitary-adrenal (HPA) axis function, the present study investigated associations between PGV development and HPA hormones that play a role in the earlier pubertal phase of adrenarche.
Participants were a community sample of 249 children and early adolescents who participated in longitudinal brain imaging and pubertal assessments. Each participant provided data at one or two waves 1.5–3 years apart, resulting in 409 datasets that covered the age range 8–13 years. PGV was estimated from T1-weighted Magnetic Resonance Imaging (MRI) scans, and dehydroepiandrosterone (DHEA), its sulfate (DHEA-S) and testosterone were measured from saliva. Estradiol was measured for a subset of females. Parents reported on physical pubertal development. Linear mixed modeling was used to investigate associations between age, pubertal measures and PGV development.
DHEA, DHEA-S and testosterone (in addition to physical maturation) explained variance in PGV development over and above age, and in a sex-dependent fashion. In all cases, associations were stronger, or only present in females. Estradiol was associated with PGV in females, but this did not appear to account for adrenarcheal hormone effects.
Our findings suggest a key role for the hormones of adrenarche, the first biochemical phase of puberty, in PGV development. Further research is required to understand the sex-specific role of adrenarcheal and gonadarcheal hormones on the PGV across development.
Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive ...disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta‐analysis. Relative to CTL, patients with adolescent‐onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first‐episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = −0.173 to −0.184). Our results suggest that previously reported MDD‐associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.
The reproducibility crisis in neuroimaging has led to an increased demand for standardized data processing workflows. Within the ENIGMA consortium, we developed HALFpipe (Harmonized Analysis of ...Functional MRI pipeline), an open‐source, containerized, user‐friendly tool that facilitates reproducible analysis of task‐based and resting‐state fMRI data through uniform application of preprocessing, quality assessment, single‐subject feature extraction, and group‐level statistics. It provides state‐of‐the‐art preprocessing using fMRIPrep without the requirement for input data in Brain Imaging Data Structure (BIDS) format. HALFpipe extends the functionality of fMRIPrep with additional preprocessing steps, which include spatial smoothing, grand mean scaling, temporal filtering, and confound regression. HALFpipe generates an interactive quality assessment (QA) webpage to rate the quality of key preprocessing outputs and raw data in general. HALFpipe features myriad post‐processing functions at the individual subject level, including calculation of task‐based activation, seed‐based connectivity, network‐template (or dual) regression, atlas‐based functional connectivity matrices, regional homogeneity (ReHo), and fractional amplitude of low‐frequency fluctuations (fALFF), offering support to evaluate a combinatorial number of features or preprocessing settings in one run. Finally, flexible factorial models can be defined for mixed‐effects regression analysis at the group level, including multiple comparison correction. Here, we introduce the theoretical framework in which HALFpipe was developed, and present an overview of the main functions of the pipeline. HALFpipe offers the scientific community a major advance toward addressing the reproducibility crisis in neuroimaging, providing a workflow that encompasses preprocessing, post‐processing, and QA of fMRI data, while broadening core principles of data analysis for producing reproducible results. Instructions and code can be found at https://github.com/HALFpipe/HALFpipe.
HALFpipe is a user‐friendly software that facilitates reproducible analysis of fMRI data, including preprocessing, single‐subject, and group analysis. It provides state‐of‐the‐art preprocessing using fMRIPrep, but removes the necessity to convert data to the BIDS format. Common resting‐state and task‐based fMRI features can then be calculated on the fly using FSL and Nipype for statistics.
Cow's milk proteins cause allergic symptoms in 2% to 3% of all infants. In these individuals, the physiological mechanism of tolerance is broken with subsequent possible sensitization to antigens, ...which can lead eventually to allergic responses. The present review aims to provide an overview of different aspects of immune modulation by dietary intervention in cow's milk allergy (CMA). It focuses on pathogenetic mechanisms of different CMA related disorders, e.g., gastroesophageal reflux and eosinophilic esophagitis, highlighting the role of dietary management on innate and adaptive immune systems. The traditional dietary management of CMA has greatly changed in the last years, moving from a passive approach, consisting of an elimination diet to relieve symptoms, to a "proactive" one, meaning the possibility to actively modulate the immune system. Thus, new insights into the role of hydrolysates and baked milk in immunomodulation are addressed here. Additionally, nutritional components, such as pre- and probiotics, may target the immune system via microbiota, offering a possible road map for new CMA prevention and treatment strategies.
Abstract Diffusion tensor imaging (DTI) allows the study of white matter (WM) structure. Literature suggests that WM structure could be altered in obsessive–compulsive disorder (OCD) proportional to ...the severity of the disease. Heterogeneity of brain imaging methods, of the studied samples, and of drug treatments make localization, nature, and severity of the WM abnormalities unclear. We applied Tract-Based Spatial Statistics (TBSS) of DTI measures to compare fractional anisotropy (FA), mean, axial, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by severe OCD (18 drug-naive, and 22 with an ongoing drug treatment) and 41 unrelated healthy volunteers from the general population. Data were analyzed accounting for the effects of multiple comparisons, and of age, sex, and education as nuisance covariates. Compared to controls, OCD patients showed a widespread reduction of FA with a concurrent increase of mean and radial diffusivity. In no brain areas patients had higher FA or lower diffusivity values than controls. These differences were observed in drug-treated patients compared to drug-naive patients and healthy controls, which in turn did not differ among themselves in any DTI measure. Reduced FA with increased mean and radial diffusivity suggests significant changes in myelination of WM tracts, without axonal loss. Drug treatments could modify the structure of cell membranes and myelin sheaths by influencing cellular lipogenesis, cholesterol homeostasis, autophagy, oligodendrocyte differentiation and remyelination. Changes of DTI measures in drug-treated OCD patients could reflect pathophysiological underpinnings of OCD, or a yet unexplored part of the mechanism of action of drugs.
Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. ...Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march.
•Longitudinal study with two waves of imaging data and observational measures of parenting.•We examined functional connectivity of amygdala and selected large-scale networks.•We detected ...developmental effects as a function of parenting.•Positive parenting was associated with decreased control network connectivity.•Positive parenting behavior may promote resting state network maturation.
Parenting behavior is associated with internalizing symptoms in children, and cross-sectional research suggests that this association may be mediated by the influence of parenting on the development of frontoamygdala circuitry. However, longitudinal studies are lacking. Moreover, there is a paucity of studies that have investigated parenting and large-scale networks implicated in affective functioning. In this longitudinal study, data from 95 (52 female) children and their mothers were included. Children underwent magnetic resonance imaging that included a 6 min resting state sequence at wave 1 (mean age = 8.4 years) and wave 2 (mean age = 9.9 years). At wave 1, observational measures of positive and negative maternal behavior were collected during mother-child interactions. Region-of-interest analysis of the amygdala, and independent component and dual-regression analyses of the Default Mode Network (DMN), Executive Control Network (ECN) and the Salience Network (SN) were carried out. We identified developmental effects as a function of parenting: positive parenting was associated with decreased coactivation of the superior parietal lobule with the ECN at wave 2 compared to wave 1. Thus our findings provide preliminary longitudinal evidence that positive maternal behavior is associated with maturation of the connectivity between higher-order control networks.
The negative impact of adverse experiences in childhood on neurodevelopment is well documented. Less attention however has been given to the impact of variations in “normative” parenting behaviors. ...The influence of these parenting behaviors is likely to be marked during periods of rapid brain reorganization, such as late childhood. The aim of the current study was to investigate associations between normative parenting behaviors and the development of structural brain networks across late childhood. Data were collected from a longitudinal sample of 114 mother-child dyads (54% female children,
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age 8.41 years, SD = 0.32 years), recruited from low socioeconomic areas of Melbourne, Australia. At the first assessment parenting behaviors were coded from two lab-based interaction tasks and structural magnetic resonance imaging (MRI) scans of the children were performed. At the second assessment, approximately 18 months later (
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age 9.97 years, SD = 0.37 years) MRI scans were repeated. Cortical thickness (CT) was extracted from T1-weighted images using FreeSurfer. Structural covariance (SC) networks were constructed from partial correlations of CT estimates between brain regions and estimates of network efficiency and modularity were obtained for each time point. The change in these network measures, from Time 1 to Time 2, was also calculated. At Time 2, less positive maternal affective behavior was associated with higher modularity (more segregated networks), while negative maternal affective behavior was not related. No support was found for an association between local or global efficacy and maternal affective behaviors at Time 2. Similarly, no support was demonstrated for associations between maternal affective behaviors and change in network efficiency and modularity, from Time 1 to Time 2. These results indicate that normative variations in parenting may influence the development of structural brain networks in late childhood and extend current knowledge about environmental influences on structural connectivity in a developmental context.
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