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• Our study unravels distinct clinical trajectories associated with PPP3CA mutations, from early-onset severe phenotypes to late-onset moderate forms, emphasizing the critical influence of mutation location within the gene on the severity of developmental and epileptic encephalopathy. • Corroborating the existing literature, our cases reaffirm the correlation between the degree of protein loss of function and the severity of PPP3CA-related DEE: missense mutations associate with milder phenotypes, while truncating mutations lead to profound disabilities and potentially fatal outcomes. • Beyond seizure types, our study meticulously characterizes the interictal EEG features associated with PPP3CA mutations: fronto-temporal interictal epileptiform discharges, hypsarrhythmia, frontal high amplitude delta activity, discontinuous activity in sleep. • PPP3CA-related DEE highlights the intricate interplay between intracellular calcium concentration, Ca2+ dependent signal transduction and epileptogenesis. The objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE). We provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain. Our in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy. Our study emphasizes the critical role of pathogenic variants' type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies. [ABSTRACT FROM AUTHOR]

Disorganization is a core dimension of schizophrenia, yet it is relatively under-investigated compared to positive and negative ones, especially at the illness onset. Indeed, most of the empirical studies investigating the disorganized domain included patients with prolonged schizophrenia. Therefore, the aims of this research were (1) to monitor the longitudinal stability of disorganized symptoms in young patients with First Episode Schizophrenia (FES) along a 2-year follow-up period, and (2) to examine any significant association of disorganization with functioning, psychopathology and the specific treatment components of an "Early Intervention in Psychosis" (EIP) program across the 2 years of follow-up. At baseline, 159 FES individuals (aged 12–35 years) completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Spearman's correlation coefficients and multiple linear regression analysis were carried out. During the follow-up period, disorganization had relevant enduring positive associations with PANSS negative symptoms, lack of judgment/insight and positive symptoms representing delusional thought contents, as well as significant enduring negative correlation with GAF scores. Along the 2 years of follow-up, FES patients also showed a relevant improvement in disorganization symptoms. This reduction was specifically associated with the number of individual psychotherapy sessions provided during the first year of treatment. Disorganization is a prominent clinical feature in FES at the recruitment in specialized EIP services, but its temporal trajectory reveals a decrease over time, together with the delivery of specific, patient-tailored EIP interventions. • Disorganization is clinically relevant already in First-Episode Schizophrenia. • Disorganization had enduring associations with negative symptoms and lack of insight. • Disorganization also had enduring correlation with functioning deterioration. • FES patients had a relevant improvement in disorganization along the 2 years of follow-up. • This overtime reduction in disorganization severity was related to individual psychotherapy. [ABSTRACT FROM AUTHOR]

Unplanned reactive aggressive acts are a clinical feature of particular interest in patients with borderline personality disorder (BPD). The early identification of personality traits correlated to aggressive behavior is certainly desirable in BDP populations. This study analyzes a clinical sample of 122 adult outpatients with BPD referred to Adult Mental Health Services of the Department of Mental Health of Bologna, in Italy. The study examines the relationship with personality facets of the DSM-5 alternative model for personality disorders (AMPD), Personality Inventory for DSM (PID-5), with respect to the four main components of aggression measured by the Aggression Questionnaire (AQ): hostility, anger, verbal and physical aggression. Using robust regression models, the relationships between PID-5 facets and domains and the aggression components under consideration were identified. Verbal and physical aggression in our sample of BPD outpatients is mainly associated to PID-5 antagonism domain. Physically aggressive behavior is also related to callousness facet. The traits most consistently associated with aggression were the domain of Antagonism and the facet of Hostility. The study findings highlight the need for clinicians working with individuals with BPD to pay particular attention to traits of hostility, callousness, and hostility to understand aggression. • Aggressive behavior in BPD outpatients is predicted by PID-5 antagonism. • Physically aggressive behavior is predicted by PID-5 callousness. • Verbal aggression by PID-5 impulsivity facet. • Clinicians working with BPD individuals should pay attention to traits of hostility and callousness to understand aggression. [ABSTRACT FROM AUTHOR]

Background Acute diplopia (AD) is an uncommon and distressing symptom of numerous ocular and neurological conditions, with potentially serious sequelaes. No data are present in pediatrics on the presentation and management of AD. Aim This study investigated characteristics, etiology and health care utilization of the pediatric population with AD accessed to pediatric Emergency Departments (ED), trying to identify “red flags” associated with potentially life -threatening (LT) conditions. Methods We conducted a cohort multicenter study on children with AD in ten Italian hospitals. Patients were classified into diagnostic categories, comparing children with and without LT disease. Results 621 children presented AD at a rate of 3.6 per 10.000. The most frequent diagnosis among no-LT conditions (81.2%) were headache, ocular disorders and minor post-traumatic disease, while LT conditions (18.8%) were represented by brain tumors, demyelinating conditions, idiopathic intracranial hypertension and major post-traumatic diseases. The LT group showed a significantly higher age, with the odds increased by 1% for each month of age. Monocular diplopia occurred in 16.1%, but unlike adult one-fifth presented LT conditions. Binocular diplopia, associated ocular manifestations or extraocular neurological signs were significantly more common in the LT group. At regression logistic analysis strabismus and ptosis were associated with LT conditions. Conclusion The majority of children presented no-LT conditions and more than one-fourth of patients had headache. Monocular diplopia in the LT group was never isolated but associated with other signs or symptoms. Our study was able to identify some specific ocular disturbances or neurologic signs potentially useful for ED physician to recognize patients with serious pathologies. [ABSTRACT FROM AUTHOR]

The term "brittle" is used to describe an uncommon subgroup of patients with type I diabetes whose lives are disrupted by severe glycaemic instability with repeated and prolonged hospitalization. Psychosocial problems are the major perceived underlying causes of brittle diabetes. Aim of this study is a systematic psychopathological and personological assessment of patients with brittle diabetes in comparison with subjects without brittle diabetes, using specific parameters of general psychopathology and personality disorders following the multi-axial format of the current DSM-IV-TR (Diagnostic and Statistical manual of Mental Disorders - IV Edition - Text Revised) diagnostic criteria for mental disorders. Patients comprised 42 subjects with brittle diabetes and a case-control group of 42 subjects with stable diabetes, matched for age, gender, years of education, and diabetes duration. General psychopathology and the DSM-IV-TR personality disorders were assessed using the Symptom Checklist-90-Revised (SCL-90-R) and the Structured Clinical Interview for axis II personality Disorders (SCID-II). The comparison for SCL-90-R parameters revealed no differences in all primary symptom dimensions and in the three global distress indices between the two groups. However, patients with brittle diabetes showed higher percentages in borderline, histrionic, and narcissistic personality disorder. In this study, patients with brittle diabetes show no differences in terms of global severity of psychopathological distress and specific symptoms of axis I DSM-IV-TR psychiatric diagnoses in comparison with subjects without brittle diabetes. Differently, individuals with brittle diabetes are more frequently affected by specific DSM-IV-TR cluster B personality disorders. [ABSTRACT FROM AUTHOR]

Background Given the rarity of this condition, especially in children, there is a paucity of large reported paediatric case series of anti-N-methyl-d-aspartate receptor encephalitis. Methods To contribute to define the features of this condition, we describe retrospectively a new nationwide case series of 20 children (50% females), referred by 13 Italian centres. Results Mean age at onset was 8 years (range 3–17). Prodromal symptoms were reported in 31.6%; onset was with neurological symptoms in 70%, and with behavioural/psychiatric disturbances in 30%. Most patients developed a severe clinical picture (90%), and 41% experienced medical complications; children 12–18 years old seemed to be more severe and symptomatic than younger patients. All children received first-line immune therapy; second-line treatment was administered to 45%. Relapses occurred in 15%. At last follow-up (mean 23.9 months, range 5–82), 85% patients had mRS 0–1; this rate was higher among older patients, and in those receiving first immune therapy within 1 month. Conclusions Our case series confirms a symptomatologic core of paediatric anti-N-methyl-d-aspartate receptor encephalitis, even though displaying some distinctive features that may be explained by a specific genetic background or by the limited number of patients. The growing incidence of this condition, the relative age-dependent variability of its manifestations, the availability of immunotherapy and the possible better outcome with early treatment impose a high index of clinical suspicion be maintained. In the absence of data suggesting other specific etiologies, paediatricians should consider this diagnosis for children presenting with neurological and/or behavioural or psychiatric disturbances, regardless of age and gender. [ABSTRACT FROM AUTHOR]

The pear crop offers an expansive market opportunity in southern Brazil, because of suitable climatic conditions and available infrastructure. However, there are still some barriers that prevent satisfactory economic production. Floral bud necrosis (FBN) is one of the main problems afflicting pear orchards in southern Brazil. FBN is characterized by the occurrence of necrosis in the flower primordia of floral buds decreasing the crop yield potential. The objective of this work was to evaluate the behavior of European pear cultivars (Clapp's Favourite, Conference, Packham's Triumph, Rocha, Abate Fetel, Santa Maria, Decana and William's) grafted on quince rootstocks (Adams, EMA and EMC) to FBN susceptibility in two different phenological stages (vegetative dormancy and green tip) and two different edaphoclimatic regions (Fraiburgo/SC and Urupema/SC) of southern Brazil during the 2009/2010 and 2010/2011 growing seasons. Twenty floral buds at both phenological stages of vegetative dormancy and green tip were collected in 10 randomized plants per plot in each region. The floral buds were assessed by microscope following the symptomatic scale of: 1. Floral buds with absence of necrosis; 2. Floral buds with partial necrosis and, 3. Floral buds with total necrosis. The combinations Conference/Adams and Packham's Triumph/EMA and the combination Abate Fetel/Adams showed the highest severity of floral bud necrosis in both phenological stages evaluated in the region of Fraiburgo/SC and Urupema/SC, respectively. The Clapp's Favourite/EMA and Conference/EMC combinations significantly showed the lowest severity of FBN in both the phenological stages of vegetative dormancy and green tip in both regions of Fraiburgo/SC and Urupema/SC, in the edaphoclimatic conditions of southern Brazil during the 2009/2010 and 2010/2011 growing seasons. [ABSTRACT FROM AUTHOR]

Purpose: Routine Outcome Monitoring (ROM) is still poorly implemented in the routine forensic psychiatric practice. As reliable ROM instruments are lacking, the aims of this research was to assess the psychometric properties of the Parma Scale (Pr-Scale) and its sensitivity to measure scores' longitudinal changes.Methods: Interrater and test-retest reliability, internal consistency and concurrent validity were investigated in offenders with mental disorder. Scores' longitudinal changeability was examined after a 3-month period using the Wilcoxon test for repeated measure.Results: Sixty male adult patients were recruited in this study. Our findings showed good to excellent interrater and test-retest reliability, concurrent validity and internal consistency for the Pr-Scale. Pr-Scale scores also display a moderate to large changeability over time.Conclusions: Our results support the clinical use of the Pr-Scale in forensic psychiatric settings as reliable ROM instrument. [ABSTRACT FROM AUTHOR]

The architectural and landscape aspects connected to tunnel portals have become very important since a new culture of environmental protection has emerged in recent years and has forced designers to better integrate infrastructure with the environment. The technical, architectural and landscape aspects of tunnel portal design are analyzed and discussed in this paper providing a systematic comparison of different architectural solutions. A design flow chart for a tunnel portal design is also presented. [Copyright &y& Elsevier]

Carotid artery (CA) dissection is a rare etiology of neonatal arterial ischemic stroke (NAIS). We describe one novel case and conduct a systematic literature review on NAIS attributed to CA dissection, to collect data on its clinical-radiological presentation, treatment, and outcome. Eight published cases of NAIS attributed to CA dissection were identified and analyzed with our case. All patients (nine of nine) were born at term, and eight of nine experienced instrumental/traumatic delivery or urgent Caesarean section. None had fetal problems during pregnancy or thrombophilia. Signs and symptoms at presentation (between days of life 0 and 6) included seizures (eight of nine), respiratory distress or irregular breathing (five of nine), hyporeactivity, decreased consciousness or irritability (four of nine), and focal neurological signs (two of nine). At magnetic resonance imaging (MRI), stroke was unilateral in seven of nine and extensive in five of nine. CA dissection was documented by neuroimaging or at postmortem studies (seven of nine), and hypothesized by the treating physicians based on delivery and neuroradiology characteristics (in the remaining two of nine). Antithrombotic treatment was used in two of nine. According to available follow-up, one of eight died at age seven days, seven of eight had neurological/epileptic sequelae, and CA recanalization occurred in three of four. NAIS attributed to CA dissection is rarely identified in the literature, often preceded by traumatic/instrumental delivery, presenting with seizures and systemic signs/symptoms, and often characterized by extensive MRI lesions and neurological sequelae. Definite evidence and recommendations on antithrombotic treatment are lacking. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is characterized by cortical tubers, determining cortical disarrangement and consequently drug-resistant epilepsy, intellectual disability, and TSC-associated neuropsychiatric disorders (TAND). To establish whether gyrification index (GI), a software-based neuroradiological parameter, could be associated with the severity of phenotype in TSC, identifying the cortical regions that are more associated with the severity of the main clinical manifestations. This was a retrospective cross-sectional study. Magnetic resonance imaging was acquired on a 1.5-T scanner. CAT12 toolbox was used for the estimation of GI. Data analysis was performed with Jamovi. The level of significance was set to P < 0.05 for all tests. Forty-five patients with TSC and 42 healthy controls were included. Patients with TSC were characterized by higher total GI (P = 0.002) compared with healthy controls. Among patients with TSC, a higher total GI was associated with impaired neurological examination (P = 0.039), epilepsy (P = 0.017), intellectual disability (P = 0.013), TAND (P = 0.013), and higher number of cortical tubers (P < 0.001). An increased local GI in specific cortical areas was associated with TAND and autism spectrum disorders. GI is a software-based neuroradiological parameter that could represent a reliable overall prognostic marker in TSC. Local GI can be used to identify phenotype-specific gyrification patterns allowing an early characterization of patients with TSC. [ABSTRACT FROM AUTHOR]

The structure and energetics of crystalline phases of poly(vinylidene difluoride) were investigated using density functional theory (DFT). In particular, we present data on non-polar analogues of the β and γ phases that have not yet been experimentally characterised. The results from a variety of exchange and correlation functionals were compared and it was found that van der Waals (vdW) interactions have an important effect on the calculated crystal structures. While the relative phase energies were not strongly dependent on the functional, the cohesive energies were significantly affected. Image 1 • Non-polar analogue of β phase, denoted ζ, characterised for the first time. • ζ structure has coplanar chains and space group Pmma. • Transition barrier from β to ζ is less than 20 kJ/mol. • Our monoclinic angle for ε phase is 90 degrees, not 120 degrees as previously reported. • Phase energies per monomer of all PVDF phases vary by less than around 10 kJ/mol [ABSTRACT FROM AUTHOR]

Objective Given the rarity of this condition, especially in children, there is a paucity of literature reporting large case series of paediatric anti-N-methyl-D-aspartate receptor encephalitis. Our goal is to contribute to define the features of paediatric anti-N-methyl-D-aspartate receptor encephalitis. Methods We describe a new nationwide case series of 20 children (50% females), referred by 13 Italian centers. Results Mean age at onset was 8 years (range 3–17). Prodromal symptoms were reported in 31.6%; onset was with neurological symptoms in 70%, and with behavioral/psychiatric disturbances in 30%. Most patients developed a severe clinical picture (90%), and 41% experienced medical complications; children 12–18 years old seemed to be more severe and symptomatic than younger patients. All children received first-line immune therapy; second-line treatment was administered to 45%. Relapses occurred in 15%. Most patients recovered substantially (80%); this rate was higher among older patients, and in those receiving first immune therapy within 1 month. Conclusion Our case series confirms a symptomatologic core of paediatric anti-N-methyl-D-aspartate receptor encephalitis, even though displaying some distinctive features that may be explained by a specific genetic background or by the limited number of the patients. The growing incidence of this condition, the relative age-dependent variability of its manifestations, the availability of immunotherapy and the possible better outcome with early treatment impose a high index of clinical suspicion be maintained. Paediatricians should consider this diagnosis for children presenting with neurological and/or behavioral or psychiatric disturbances, regardless of age and gender, especially in the absence of data suggesting other specific etiologies. Other authors: F. Beccaria, L. Giunta, C. Boniver, M.G. Natali Sora, N. Zamponi. [ABSTRACT FROM AUTHOR]

Objective To describe the natural history of sporadic and familial hemiplegic migraines (SHM and FHM) with onset in the pediatric age. Methods Retrospective observational study of 28 cases, visiting 9 Italian Centers for Juvenile Headache, diagnosed as SHM or FHM (ICHD-III b version, 2013) with onset under 16 years and with a longitudinal follow-up. Results 28 cases (17 females, 11 males): 23 SHM (14 females, 9 male), 5 FHM (3 females, 2 male). Family history was positive for migraine without aura (5/28) or with aura non hemiplegic (8/28). Triggering factors were found in 13/28 cases. Age at HM onset: mean 10.1 y, range 4–16 y (5/28 cases under 6 y). Mean duration of aura was 11h 13' (range 5′–48 h). Between HM attacks, neurologic examination was normal in 26/28 cases. At follow-up: mean age 16.9 y (range 6.5–47 y), mean duration of follow-up 8.1 y (range 2.5–38 y). The frequency of attacks ranged from 2 per month to less than 1 per year (mean 5–6 every year). During follow-up, FHM and SHM cases showed some differences: in cases with SHM attacks were less frequent but more severe while FHM patients had less intense but more frequent attacks and also a longer duration of disease. Preventive therapy for HM was prescribed to 12/28 cases. Conclusion In the Literature data on the natural history of HM are quite limited, particularly in children. In the majority of our cases, the frequency and the type of attacks were quite variable, and in less than half of the cases trigger factors were identified. The majority of our patients had a good prognosis, even in cases with early onset of HM and/or prolonged and/or severe HM attacks. The natural history of SHM seems to differ from the FHM. [ABSTRACT FROM AUTHOR]

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To clarify the most frequent modalities of use of plasma exchange (PE) in pediatric anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis and to establish the most effective association with other immunotherapies. METHODS: Systematic literature review on PE in pediatric anti-NMDAR encephalitis (2007-2015). RESULTS: Seventy-one articles were included (mostly retrospective), reporting a total of 242 subjects (73.2%, 93/127 females; median age at onset 12years, range 1-18). Median time to immunotherapy was 21days (range 0-190). In most cases, PE was given with steroids and IVIG (69.5%, 89/128), or steroids only (18%, 23/128); in a minority, it was associated with IVIG only (7%, 9/128), or was the only first-line treatment (5.5%, 7/128). In 54.5% (65/119), PE was the third treatment after steroids and IVIG, in 31.1% (37/119) the second after steroids or IVIG; only in 14.3% (17/119) was it the first treatment. Second-line immunotherapies were administered in 71.9% (100/139). Higher rates of full/substantial recovery at follow-up were observed with immunotherapy given ?30days from onset (69.4%, 25/36) compared to later (59.2%, 16/27), and when PE was associated with steroids (66.7%, 70/105) rather than not (46.7%, 7/15). Significant adverse reactions to PE were reported in 6 patients. CONCLUSION: Our review disclosed a paucity of quality data on PE in pediatric anti-NMDAR encephalitis. PE use in this condition has been increasingly reported, most often with steroids and IVIG. Despite the limited number of patients, our data seem to confirm the trend towards a better outcome when PE was administered early, and when given with steroids. [ABSTRACT FROM AUTHOR]

Abstract: Brain atrophy has consistently been observed in schizophrenia, representing a ‘gross’ evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age±SD=39.19±12.20 years; 34 males, 20 females) and 24 normal controls (mean age±SD=44.63±10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160ms, TE=47ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/So×100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p =0.02) and inverse CE laterality index (p =0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia. [Copyright &y& Elsevier]