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Introduction Psychosis onset typically occurs during adolescence or early adulthood, coinciding with the latest stage of brain maturation. Alterations in brain functional connectivity (FC) accompany the emergence of psychiatric symptoms and cognitive impairments. Thus, age-related FC changes may be informative regarding psychosis onset. Objectives We defined neurotypical age-related FC trajectories and hypothesized that FC of individuals at familial and clinical high risk (HR) for psychosis deviates from FC of neurotypical controls (NC). Methods We analyzed two independent cohorts, of (a) 356 early adult NC (yNC; age=22±2y, m:f=149:207), and 127 mature adult NC (aNC; age=38±7y, m:f=79:48), and (b) 92 yNC (age=22±2y, m:f=34:58), 33 aNC (age=36±6y, m:f=21:12), 38 early HR adults (age=20±3y, m:f=18:20). We acquired fMRI data from multiple scans (resting-state, working memory, episodic memory, and implicit emotion processing). FC was obtained by computing Pearson’s correlations between time-courses of every independent component (IC) defined by an Independent Component Analysis approach (NeuroMark). Age-varying components of interest (yNC/aNC differences on FC based on linear mixed effect regressions) were tested for differences between HR and yNC through the Wilcoxon rank-sum test. Results showed age-related FC differences (yNC/aNC) in a set of 17 IC pairs (pFDR0.05). Conclusions This study tested FC alterations associated with the risk for psychosis and highlighted the relationship between psychosis and potentially altered brain functional processes. Disclosure No significant relationships.

Haematite (α-Fe2O3) nanostructures were synthesized via a Pechini sol–gel method (PSG) and an electrospinning (ES) technique. Their texture and morphology were investigated by scanning and transmission electron microscopy. α-Fe2O3 nanoparticles were obtained by the PSG method, whereas fibrous structures consisting of interconnected particles were synthesized through the ES technique. The crystallinity of the α-Fe2O3 nanostructures was also studied by means of x-ray diffraction and Raman spectroscopy. Gas-sensing devices were fabricated by printing the synthesized samples on ceramic substrates provided with interdigitated Pt electrodes. The sensors were tested towards low concentrations of ethanol in air in the temperature range (200−400°C). The results show that the α-Fe2O3 nanostructures exhibit somewhat different gas-sensing properties and, interestingly, their sensing behaviour is strongly temperature-dependent. The availability of active sites for oxygen chemisorption and the diffusion of the analyte gas within the sensing layer structure are hypothesized to be the key factors responsible for the different sensing behaviour observed. [ABSTRACT FROM AUTHOR]

The phenomenon known as "dimming" or shading, caused by the increase in aerosols, air pollutants, and population density, is reducing global radiation, including both direct solar radiation and radiation scattered by the atmosphere. This phenomenon poses a significant challenge for agricultural production in many regions worldwide, with a global radiation decrease estimated between 1.4% and 2.7% per decade in areas between 25° N and 45° N. In particular, in Mediterranean regions, the production of durum wheat ( Triticum turgidum L. subsp. Durum ) is increasingly constrained by abiotic factors, such as spring/summer heat stress and drought, as well as reductions in solar radiation. Field experiments were conducted in Mosciano Sant'Angelo, Italy, over two cropping seasons (2016-2017 and 2017-2018) to evaluate the effects of photosynthetically active radiation (PAR) availability and nitrogen (N) fertilization on durum wheat. A split-plot design was used with two PAR levels (100% and 20% PAR) and three N rates (0, 100, and 250 kg ha -1 ). Results highlighted that full sunlight (NoSh) significantly increased grain yield (+25%), thousand kernel weight (+46%), and total gluten fractions (+16%) compared to shaded conditions (Sh). Chlorophyll content and NDVI values were highest under Sh combined with 250 kg N ha -1 . Rainfall patterns strongly influenced productivity, with better vegetative growth in 2016-2017 and improved grain filling in 2017-2018. Nitrogen application significantly enhanced grain protein content, particularly under arid conditions. These findings emphasize the interaction between light availability and nitrogen management, suggesting that optimizing these factors can improve yield and quality in durum wheat under Mediterranean conditions.

The aim of this study was to examine the neurocognitive deficits associated with the first episode of major depressive disorder (recent onset depression, ROD) in adolescents as compared to adult patients. Cross-sectional neurocognitive data from the baseline assessments of the PRONIA study with N = 650 (55.31% females) were analyzed. Based on a principal component analysis of eleven neurocognitive tests, we constructed an overall neurocognitive performance (NP) score. We examined mean score differences in NP between the groups of healthy controls (HC) and ROD and between adolescents (15-21 years) and adults (22-40 years) within a GLM approach. This accounts for unbalanced data with focus on interaction effects while controlling for effects of medication and educational years. Our results show lower NP for the ROD as compared to the HC group (d = - 0.29, p = .046) and lower NP for the adolescent group as compared to the adult group (d = - 0.29; p < .039). There was no interaction between these two group effects (F = 1.11; p = .29). Our findings suggest that the detrimental effect of ROD on neurocognitive functioning is comparable in adolescent and adult patients, since lower scores in adolescent patients are explained by effects of age and education. Neurocognitive impairment is an under addressed issue in clinical treatment guidelines for adolescent MDD. We suggest efficient monitoring in clinical practice by using an aggregate of the Digit Symbol Substitution Test and the Trail Making Test B, which highly correlated with the overall score of NP (r = 0.82)., (© 2024. The Author(s).)

Purpose: Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T-cell response to overcome tumor heterogeneity. NOUS-PEV is a vector-based personalized vaccine, expressing 60 nAgs and consists of priming with a nonhuman Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara. Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment-naïve patients with metastatic melanoma (NCT04990479)., Patients and Methods: The feasibility of this approach was demonstrated by producing, releasing, and administering to 6 patients 11 of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration., Results: The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen-specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced T-cell receptor (TCR) clonotypes was observed in the posttreatment biopsies of patients with clinical response, providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cells., Conclusions: These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor-reactive T cells to empower a diverse, potent, and durable antitumor immune response. Finally, a gene signature indicative of the reduced presence of activated T cells together with very poor expression of the antigen-processing machinery genes has been identified in pretreatment biopsies as a potential biomarker of resistance to the treatment., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. While studies have primarily focused on identifying risk factors for disease progression, very few data exist on the likelihood of achieving complete recovery from the disease., Methods: We conducted a single-center retrospective study on all consecutive patients with biopsy-proven IgAN diagnosed between 1986 and 2018 in our pediatric center. Biopsies were classified according to the MEST-C Oxford classification score. "Complete clinical remission" was defined as the absence of proteinuria, hematuria, and hypertension in patients with normal kidney function who had been off therapy for more than 2 years., Results: Overall, 153 patients with age at onset of 10.6 ± 4 years were enrolled in the study. Of these, 41 achieved "complete clinical remission." The estimated probability of complete clinical remission at 10 years was 43% (95%CI 33-54). However, seven patients relapsed within 10 years. Multivariable analysis showed that higher age at onset (HR 0.89, 95%CI 0.80-0.98, p = 0.017) and segmental glomerulosclerosis lesions (HR 0.28, 95%CI 0.10-0.79, p = 0.017) decreased significantly the chances of achieving complete clinical remission. Immunosuppressive therapy was not significantly associated with clinical outcomes., Conclusions: Approximately one-third of patients with pediatric-onset IgAN achieve prolonged remission, in particular, very young children at disease onset without sclerotic glomerular lesions. Longer term follow-up is needed to assess if these patients have achieved permanent remission., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

In fatty acid photodecarboxylase (FAP), light-induced formation of the primary radical product RCOO⋅ from fatty acid RCOO - occurs in 300 ps, upon which CO 2 is released quasi-immediately. Based on the hypothesis that aliphatic RCOO⋅ (spectroscopically uncharacterized because unstable) absorbs in the red similarly to aromatic carbonyloxy radicals such as 2,6-dichlorobenzoyloxy radical (DCB⋅), much longer-lived linear RCOO⋅ has been suggested recently. We performed quantum chemical reaction pathway and spectral calculations. These calculations are in line with the experimental DCB⋅ decarboxylation dynamics and spectral properties and show that in contrast to DCB⋅, aliphatic RCOO⋅ radicals a) decarboxylate with a very low energetic barrier and on the timescale of a few ps and b) exhibit little red absorption. A time-resolved infrared spectroscopy experiment confirms very rapid, ≪300 ps RCOO⋅ decarboxylation in FAP. We argue that this property is required for the observed high quantum yield of hydrocarbons formation by FAP., (© 2024 Wiley‐VCH GmbH.)

Historically, the complement system (classical, lectin, alternative, and terminal pathways) is known to play a crucial role in the etiopathogenesis of many kidney diseases. Direct or indirect activation in these settings is revealed by consumption of complement proteins at the serum level and kidney tissue deposition seen by immunofluorescence and electron microscopy. The advent of eculizumab has shown that complement inhibitors may improve the natural history of certain kidney diseases. Since then, the number of available therapeutic molecules and experimental studies on complement inhibition has increased exponentially. In our narrative review, we give a summary of the main complement inhibitors that have completed phase II and phase III studies or are currently used in adult and pediatric nephrology. The relevant full-text works, abstracts, and ongoing trials (clinicaltrials.gov site) are discussed. Data and key clinical features are reported for eculizumab, ravulizumab, crovalimab, avacopan, danicopan, iptacopan, pegcetacoplan, and narsoplimab. Many of these molecules have been shown to be effective in reducing proteinuria and stabilizing kidney function in different complement-mediated kidney diseases. Thanks to their efficacy and target specificity, these novel drugs may radically improve the outcome of complement-mediated kidney diseases, contributing to an improvement in our understanding of their underlying pathophysiology., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Inflammation is an essential defense mechanism in which innate immune cells are coordinately activated on encounter of harmful stimuli, including pathogens, tissue injury, and toxic compounds and metabolites to neutralize and eliminate the instigator and initiate healing and regeneration. Properly terminated inflammation is vital to health, but uncontrolled runaway inflammation that becomes chronic begets a variety of inflammatory and metabolic diseases and increases cancer risk. Making damaged tissues behave as "wounds that do not heal" and sustaining the production of growth factors whose physiologic function is tissue healing, chronic inflammation accelerates cancer emergence from premalignant lesions. In 1863, Rudolf Virchow, a leading German pathologist, suggested a possible association between inflammation and tumor formation, but it took another 140 years to fully elucidate and appreciate the tumorigenic role of inflammation. Key findings outlined molecular events in the inflammatory cascade that promote cancer onset and progression and enabled a better appreciation of when and where inflammation should be inhibited. These efforts triggered ongoing research work to discover and develop inflammation-reducing chemopreventive strategies for decreasing cancer risk and incidence., (©2024 American Association for Cancer Research.)

Tumor neoantigens (nAg) represent a promising target for cancer immunotherapy. The identification of nAgs that can generate T-cell responses and have therapeutic activity has been challenging. Here, we sought to unravel the features of nAgs required to induce tumor rejection. We selected clinically validated Great Ape-derived adenoviral vectors (GAd) as a nAg delivery system for differing numbers and combinations of nAgs. We assessed their immunogenicity and efficacy in murine models of low to high disease burden, comparing multi-epitope versus mono-epitope vaccines. We demonstrated that the breadth of immune response is critical for vaccine efficacy and having multiple immunogenic nAgs encoded in a single vaccine improves efficacy. The contribution of each single neoantigen was examined, leading to the identification of 2 nAgs able to induce CD8+ T cell-mediated tumor rejection. They were both active as individual nAgs in a setting of prophylactic vaccination, although to different extents. However, the efficacy of these single nAgs was lost in a setting of therapeutic vaccination in tumor-bearing mice. The presence of CD4+ T-cell help restored the efficacy for only the most expressed of the two nAgs, demonstrating a key role for CD4+ T cells in sustaining CD8+ T-cell responses and the necessity of an efficient recognition of the targeted epitopes on cancer cells by CD8+ T cells for an effective antitumor response. This study provides insight into understanding the determinants of nAgs relevant for effective treatment and highlights features that could contribute to more effective antitumor vaccines. See related Spotlight by Slingluff Jr, p. 382., (©2024 The Authors; Published by the American Association for Cancer Research.)

Symptom heterogeneity characterizes psychotic disorders and hinders the delineation of underlying biomarkers. Here, we identify symptom-based subtypes of recent-onset psychosis (ROP) patients from the multi-center PRONIA (Personalized Prognostic Tools for Early Psychosis Management) database and explore their multimodal biological and functional signatures. We clustered N = 328 ROP patients based on their maximum factor scores in an exploratory factor analysis on the Positive and Negative Syndrome Scale items. We assessed inter-subgroup differences and compared to N = 464 healthy control (HC) individuals regarding gray matter volume (GMV), neurocognition, polygenic risk scores, and longitudinal functioning trajectories. Finally, we evaluated factor stability at 9- and 18-month follow-ups. A 4-factor solution optimally explained symptom heterogeneity, showing moderate longitudinal stability. The ROP-MOTCOG ( Motor/Cognition ) subgroup was characterized by GMV reductions within salience, control and default mode networks, predominantly throughout cingulate regions, relative to HC individuals, had the most impaired neurocognition and the highest genetic liability for schizophrenia. ROP-SOCWD ( Social Withdrawal ) patients showed GMV reductions within medial fronto-temporal regions of the control, default mode, and salience networks, and had the lowest social functioning across time points. ROP-POS ( Positive ) evidenced GMV decreases in salience, limbic and frontal regions of the control and default mode networks. The ROP-AFF ( Affective ) subgroup showed GMV reductions in the salience, limbic, and posterior default-mode and control networks, thalamus and cerebellum. GMV reductions in fronto-temporal regions of the salience and control networks were shared across subgroups. Our results highlight the existence of behavioral subgroups with distinct neurobiological and functional profiles in early psychosis, emphasizing the need for refined symptom-based diagnosis and prognosis frameworks., Competing Interests: Conflict of Interest/Financial disclosure Dr Bertolino reports speaker fees from Otsuka, Lundbeck, Angelini and Rovi outside of the submitted work. Dr Hietala reports personal fees from Orion ltd, personal fees from Lundbeck, personal fees from Otsuka and other from Takeda during the conduct of the study. Dr Koutsouleris, Dr Ruhrmann, Dr Riecher-Rossler report grants from European Union over the duration of the study. Dr Meisenzahl and Dr Koutsouleris hold patent US20160192889A1 (‘Adaptive pattern recognition for psychosis risk modelling’). Dr Koutsouleris reports speaker fees from Otsuka, Roche and Angelini outside of the submitted work. Dr Pantelis reports grants from Australian NHMRC during the study, and personal fees from Lundbeck, Australia Pty Ltd outside the submitted work. Dr Upthegrove reports speaker fees from Sunovion, Otsuka and Vitaris outside the submitted work as well as unpaid officership with the British Association for Pharmacology - Honorary General Secretary 2021–2024. She serves as Deputy Editor for The British Journal of Psychiatry. Dr Falkai reports he has received research support/honoraria for lectures or advisory activities from Boehringer-Ingelheim, Janssen, Lundbeck, Otsuka, Recordati and Richter outside the submitted work. Dr Pantelis was supported by an Australian National Health and Medical Research Council (NHMRC) L3 Investigator Grant (1196508) outside the submitted work. Dr Lana Kambeitz-Ilankovic reports receiving a NARSAD Young Investigator Award of the Brain & Behavior Research Foundation No° 28474 (PI: LK-I) outside the submitted work. Dr Milaneschi reports consulting fees from Noema Pharma outside the submitted work. Dr Upthegrove reports support from the UK NIHR Oxford Health Biomedical Research Centre. The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. All other co-authors did not report any other financial disclosures or other conflicts of interests within or outside of the scope of the submitted work.

Background: Community ambulation ability is one of the most important functional loss after stroke. The assessment of the level of community walking plays an important role in the multidimensional bio-psycho-social approach, to improve quality of life and social participation of stroke survivors. The modified Functional Walking Categories (mFWC) is a worldwide widely used tool to assess community ambulation in stroke survivors, but no Italian version is yet available., Objective: To cross-culturally adapt the mFWC into Italian and to assess its validity and reliability., Methods: According to the international guidelines, a multistep translation and cultural adaptation were conducted and revised by a committee of experts. Patients admitted to intensive inpatient rehabilitation with a sub-acute stroke were recruited. Inter- and intra-rater reliability and construct validity were studied., Results: Sixty patients with sub-acute stroke were prospectively enrolled in this study. Findings showed almost perfect intra- and inter-rater reliability (k = 1.000 [95% CI 1.000-1.000] and k = 0.984 [95% CI 0.955-1.000], respectively). The construct validity of the scale was satisfactory, as 100.0% a-priori hypotheses were met., Conclusions: The Italian mFWC offers a valid tool for measuring community ambulation in stroke patients. Our work provides a validated and a cross-cultural adapted Italian version of the mFWC to accurately measure community ambulation both in clinical and research settings in Italy.

Background: Regional citrate anticoagulation (RCA) is the preferred modality of anticoagulation used in continuous kidney replacement therapy (CKRT) in adults and less extensively in children. Potential metabolic complications limit widespread use in infants, neonates, and in children with liver failure., Methods: We report our experience with a simplified protocol in 50 critically ill children, infants, and neonates, some of them with liver failure, with commercially available solutions containing phosphorous and higher concentration of potassium and magnesium., Results: RCA allowed attainment of a mean filter lifetime of 54.5 ± 18.2 h, 42.5% of circuits lasted more than 70 h, and scheduled change was the most frequent cause of CKRT interruption. Patient Ca ++ and circuit Ca ++ were maintained in the target range with mean values of 1.15 ± 0.13 mmol/l and 0.38 ± 0.07 mmol/l, respectively. No session had to be stopped because of metabolic complications. The most frequent complications were hyponatremia, hypomagnesemia, and metabolic acidosis mostly related to primary disease and critical illness. No session had to be stopped because of citrate accumulation (CA). Transitory CA occurred in 6 patients and was managed without requiring RCA interruption. No patients with liver failure presented CA episodes., Conclusions: In our experience, RCA with commercially available solutions was easily applied and managed in critically ill children, even in patients with low weight or with liver failure. Solutions containing phosphate and higher concentrations of magnesium and potassium allowed reduction of metabolic derangement during CKRT. Prolonged filter life was ensured with no detrimental effects on patients and reduced staff workload. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The best treatment for IgAN is still debated. The trials NEFIGAN and NEFIGARD have demonstrated that TRF-budesonide (Nefecon) efficiently and safely reduced proteinuria in adults, leading to FDA approval of Nefecon for adult IgAN. In pediatric IgAN, an etiological treatment does not yet exist, and the main therapies remain RAAS inhibitors and oral steroids. To our knowledge, this is one of the few pediatric reports of TRF-budesonide therapy., Case Report-Diagnosis/treatment: A 13-year-old boy underwent a kidney biopsy for recurrent macrohematuria and proteinuria, resulting in an IgAN diagnosis (MEST-C score M1-E1-S0-T0-C1). At admission, serum creatinine and UPCR were slightly increased. Three methylprednisolone pulses were performed, followed by prednisone and RAAS inhibitors therapy. However, after 10 months, macrohematuria became constant, and UPCR increased. A new kidney biopsy was performed, showing an increase in sclerotic lesions. Prednisone was discontinued, and a trial with IBD TRF-budesonide 9 mg/day started. One month later, macrohematuria episodes disappeared and UPCR decreased, with a stable kidney function. After 5 months, due to a reduction in morning cortisol levels and difficulty in drug provisioning, we started to wean TRF-budesonide by 3 mg every 3 months, with complete withdrawal after 1 year. During this period, episodes of macrohematuria dramatically decreased, and UPCR and kidney function were maintained stable., Conclusion: Our case demonstrates that TRF-budesonide could be considered an effective second-line treatment in pediatric IgAN, particularly when a long course of steroids is necessary to control active inflammation. However, pediatric clinical trials to identify the correct dosage and tolerability of TRF-budesonide are urgently needed., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.

Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures derived from cells that are released by all cell types, including brain cells. EVs are now thought to be an additional mechanism of intercellular communication. Both under normal circumstances and following the addition of proinflammatory stimuli, microglia release EVs, but the contents of these two types of EVs are different. Microglia are considered the brain-resident immune cells that are involved in immune surveillance and inflammatory responses in the central nervous system. In this research, we have analyzed the effects of EVs isolated from microglia in response to LPS (Lipopolysaccharide) on microglia activation. The EVs produced as result of LPS stimulation, knows as EVs-LPS, were then used as stimuli on microglia BV2 resting cells in order to investigate their ability to induce microglia to polarize towards an inflammatory state. After EVs-LPS stimulation, we analyzed the change to BV2 cells' morphology, proliferation, and migration, and investigated the expression and the release of pro-inflammatory cytokines. The encouraging findings of this study showed that EVs-LPS can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. This study has confirmed the critical role of EVs in communication and shown how EVs produced in an inflammatory environment can exacerbate the inflammatory process by activating microglia, which may have an impact on all brain cells., Competing Interests: The authors declare no conflicts of interest.

Purpose: Participation needs to be assessed objectively, to state accurate rehabilitation objectives. The Frenchay Activities Index (FAI) is a widely used tool to measure participation in stroke patients. To date, no cross-culturally validated Italian version of FAI is available. This study provides a translation and cross-cultural adaptation of FAI into Italian, assessing its validity and reliability in sub-acute stroke patients., Methods: According to international guidelines, a multistep translation and cultural adaptation protocol of forward and backward translations was conducted by qualified linguists and independent native English translators and revised by a healthcare committee. Patients admitted to intensive inpatient rehabilitation after stroke were recruited. Structural validity, reliability (internal consistency, inter- and intra-rater reliability and measurement error), and construct validity were studied., Results: One hundred and seventy-three patients were included in this study. No significant observations in terms of comprehensibility and conceptual equivalence of the FAI Italian version emerged. The exploratory factorial analysis revealed the presence of two subscales (i.e., domestic chores and work/leisure). The internal consistency resulted good for the first and second subscale (α = 0.821 and 0.716, respectively). Intra- and inter-reliability showed an ICC > 0.90 for both subscales. SEM = 5.75% and 2.33% and MDC = 15.85% and 6.48% were found for the first and second subscale, respectively. Construct validity of first subscale was satisfactory, as 100.0% a priori hypotheses were met, while for the second subscale it was moderate, as 66.6% a priori hypotheses were respected., Conclusion: FAI-I provides a tool for professionals to measure participation in Italian stroke patients in health and social care settings., (© 2022. Fondazione Società Italiana di Neurologia.)

High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Immunotherapy is based on different techniques aimed to redirect the patient own immune system to fight specifically cancer cells. In particular, T-lymphocytes can be genetically modified to express chimeric proteins, known as chimeric antigen receptors (CARs), targeting selected tumor-associated antigens (TAA). Disialoganglioside GD2 (GD-2) and B7-H3 are highly expressed on pHGGs and have been evaluated as possible targets in pediatric clinical trials, in addition to the antigens common to adult glioblastoma - such as interleukin-13 receptor alpha 2 (IL-13α2), human epidermal growth factor receptor 2 (HER-2) and erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2). CAR-T therapy has shown promise in preclinical model of pHGGs but failed to achieve the same success obtained for hematological malignancies. Several limitations, including the immunosuppressive tumor microenvironment (TME), the heterogeneity in target antigen expression and the difficulty of accessing the tumor site, impair the efficacy of T-cells. pHGGs display an immunologically cold TME with poor T-cell infiltration and scarce immune surveillance. The secretion of immunosuppressive cytokines (TGF-β, IL-10) and the presence of immune-suppressive cells - like tumor-associated macrophages/microglia (TAMs) and myeloid-derived suppressor cells (MDSCs) - limit the effectiveness of immune system to eradicate tumor cells. Innovative immunotherapeutic strategies are necessary to overcome these hurdles and improve ability of T-cells to eradicate tumor. In this review we describe the distinguishing features of HGGs of the pediatric population and of their TME, with a focus on the most promising CAR-T therapies overcoming these hurdles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Antonucci, Canciani, Mastronuzzi, Carai, Del Baldo and Del Bufalo.)

Background: Periprosthetic femoral fractures are challenging complications of hip arthroplasty. They are supposed to be a rare complication, but their incidence is rapidly increasing. Surgical treatment aims to achieve early mobilization and avoid the complications of prolonged bed rest. Aim of this study is to evaluate the clinical outcomes of surgical treatment comparing two surgical approaches: revision arthroplasty (RA) versus open reduction and internal fixation (ORIF)., Methods: Authors retrospectively reviewed a series of 117 patients with total hip arthroplasty treated for periprosthetic femur fractures in the period between January 2013 and March 2018 at a single tertiary referral center. Of these, 70 patients satisfied strict inclusion criteria. Patients were classified according to the Unified Classification System (UCS) and distributed in two groups according to surgical treatment. Clinical outcomes were assessed using the Oxford Hip recorded preoperatively and post operatively, Barthel Score, CIRS score (Cumulative illness rating scale), type of fracture and post-operative complications with a minimum follow up of 1 year., Results: Nominal univariate statistical analysis revealed significant differences between the post and pre-operative Oxford Hip Score (Δ Oxford) and the surgical treatment (p = 0.008) and CIRS score (p = 0.048). Moreover, we observed a significant relationship between type of treatment and type of fracture (p = 0.0001). Multivariate analyses revealed that CIRS score was independently associated with Oxford Score improvement after surgery (p = 0.024)., Conclusions: Data from this case series confirmed that surgical treatment was correlated to type of fracture, according to UCS classification. Patients treated by RA had a better functional outcome than patients treated with ORIF, but these results are strongly influenced from the patients' age, Barthel index and CIRS score. Also, authors found a correlation between functional outcome and comorbidities evaluated by CIRS score. Based on these data we suggest a multimodal approach to these patients, like those used for proximal femoral fractures., (© 2022. The Author(s).)

Background: The COVID-19 pandemic and associated public health measures have had a profound impact on health systems worldwide. The aim of this study was to assess quantitative and qualitative changes in Pediatric Emergency Department (PED) visits in Sardinia, Italy, during the early period of the COVID-19 pandemic., Methods: We retrospectively investigated the number and characteristics of visits to two major Sardinian PEDs, in the periods January-June 2020 and January-June 2019., Results: From January to June 2020, 8399 PED visits with 1160 hospital admissions (13.8% of PED visits) were registered, compared with 15,692 PED visits (Δ = -46.5%) and 1819 hospital admissions (11.6% of PED visits) occurring from January to June 2019. Comparing January-June 2020 with January-June 2019, we found differences in the percentage of visits for age groups, and significant changes in the proportion of triage codes, with a decrease in green codes (72.1% vs 74.2%, respectively) and an increase in white codes (19.0% vs 16.5%, respectively). Moreover, in the period January-June 2020, the frequency of skin disorders and acute respiratory disease significantly decreased, while the frequency of trauma, acute surgical disease, intoxication, and neuropsychiatric disease significantly increased., Conclusions: After the beginning of the Italian lockdown, we observed a marked drop in the number of PED visits, an increase in hospital admission rate, and radical changes in the reason for visit., (© 2022. The Author(s).)

Background: Brain death secondary to traumatic brain injury is one of the main sources of organs for transplantation but it can be associated with disseminated intravascular coagulation, which has been considered a relative contraindication for kidney donation., Methods: We describe two successful pediatric cases of kidney transplantation from a single donor with disseminated intravascular coagulation., Results: A 17-year-old male donor died from head injury and both kidneys were offered to our center. Within 24 h, donor's Hb and platelets dropped to 8.3 g/dl and 32 000/mcl, respectively, serum creatinine reached 2.01 mg/dl, and urinalysis showed proteinuria (300 mg/dl). Pre-implant biopsy showed massive occlusion of glomerular capillaries by fibrin thrombi containing fragmented red blood cells and inflammatory cells, and acute tubular damage. Arterioles and small arteries were spared. A diagnosis of DIC was made. The kidneys were transplanted in a 16-year-old girl and a 13-year-old boy. Slow recovery of graft function was observed in both recipients. On post-operative day 3, platelets dropped to a minimum value of 66 000 and 86 000/mcl, respectively. Diuresis was always present. On day 4, platelets started to rise. Six months later, both recipients attained normal renal function. A six-month protocol biopsy showed no microthrombi or other signs of disseminated intravascular coagulation., Conclusions: Despite the limited data available in literature, the outcome of these two cases is positive. Thus, pre-implant kidney biopsy, even if it reveals massive thrombotic occlusion of glomerular capillaries compatible with diagnosis of disseminated intravascular coagulation, should not be considered an absolute contraindication to transplantation., (© 2021 Wiley Periodicals LLC.)

Insecure attachment has been suggested as a major risk factor for mental health problems as well as a key element for the development and trajectory of psychiatric disorders. The aim of this meta-analysis was to assess whether insecure attachment constitutes a global transdiagnostic risk factor in bipolar disorder, depression, and schizophrenia spectrum disorders. We conducted a PRISMA-based systematic quantitative review to explore the prevalence of insecure attachment among patients of three representative psychiatric disorders - major depression, schizophrenia spectrum disorders and bipolar disorder - in comparison with healthy controls (HC) from a transdiagnostic point of view. Effect sizes on differences of anxious, avoidant and insecure prevalence were calculated based on 40 samples including a total of n = 2927 individuals. Overall, results indicated a large effect on prevalence of insecure attachment across all disorders compared to HC (k = 30, g = 0.88, I 2  = 71.0%, p < 0.001). In a transdiagnostic comparison, the only difference was found in avoidant attachment, which was significantly lower (p = 0.04) compared to HC in the schizophrenia spectrum disorder subgroup (k = 10, g = 0.31, I 2  = 76.60%, p < 0.0001) than the depression subgroup subgroup (k = 12, g = 0.83, I 2  = 46.65%, p < 0.0001). The lack of further transdiagnostic differences between three distinct psychiatric disorders corroborates insecure attachment as a general vulnerability factor to psychopathology. Our findings warrant further investigations, which should explore the pathways from attachment insecurity towards psychopathology. Insecure attachment likely has implications on assessment, prediction and treatment of psychiatric patients., (Copyright © 2021. Published by Elsevier Ltd.)

Infant botulism (IB) is defined as a potentially life-threatening neuroparalytic disorder affecting children younger than 12 months. It is caused by ingestion of food or dust contaminated by Clostridium botulinum spores, which germinate in the infant's large bowel and produce botulinum neurotoxin. Although the real impact of IB is likely underestimated worldwide, the USA has the highest number of cases. The limited reporting of IB in many countries is probably due to diagnostic difficulties and nonspecific presentation. The onset is usually heralded by constipation, followed by bulbar palsy, and then by a descending bilateral symmetric paralysis; ultimately, palsy can involve respiratory and diaphragmatic muscles, leading to respiratory failure. The treatment is based on supportive care and specific therapy with Human Botulism Immune Globulin Intravenous (BIG-IV), and should be started as early as possible. The search for new human-like antibody preparations that are both highly effective and well tolerated has led to the creation of a mixture of oligoclonal antibodies that are highly protective and can be produced in large quantities without the use of animals. Ongoing research for future treatment of IB involves the search for new molecular targets to produce a new generation of laboratory-produced antitoxins, and the development of new vaccines with safety and efficacy profiles that can be scaled up for clinical use. This narrative literature review aims to provide a readable synthesis of the best current literature on microbiological, epidemiological and clinical features of IB, and a practical guide for its treatment.

The early secretory pathway and autophagy are two essential and evolutionarily conserved endomembrane processes that are finely interlinked. Although growing evidence suggests that intracellular trafficking is important for autophagosome biogenesis, the molecular regulatory network involved is still not fully defined. In this study, we demonstrate a crucial effect of the COPII vesicle-related protein TFG (Trk-fused gene) on ULK1 puncta number and localization during autophagy induction. This, in turn, affects formation of the isolation membrane, as well as the correct dynamics of association between LC3B and early ATG proteins, leading to the proper formation of both omegasomes and autophagosomes. Consistently, fibroblasts derived from a hereditary spastic paraparesis (HSP) patient carrying mutated TFG (R106C) show defects in both autophagy and ULK1 puncta accumulation. In addition, we demonstrate that TFG activity in autophagy depends on its interaction with the ATG8 protein LC3C through a canonical LIR motif, thereby favouring LC3C-ULK1 binding. Altogether, our results uncover a link between TFG and autophagy and identify TFG as a molecular scaffold linking the early secretion pathway to autophagy., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)