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234 result(s) for "Longo, Chiara"
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Cognitive reorganization in patients with Parkinson’s Disease and Mild Cognitive Impairment: a neuropsychological network approach
Parkinson’s Disease (PD) exhibits heterogeneous cognitive deficits that may represent different cognitive phenotypes. While previous studies have described them in a “macro” manner, only one study has applied Network Analysis (NA) in PD. NA represents a model to explore relationships between cognitive abilities, aiding in understanding cognitive phenotypes. This study aims to verify whether the cognitive system undergoes reorganization in PD with Mild Cognitive Impairment (PD-MCI) patients. To explore this, a Level II cognitive assessment was administered to 275 PD patients, who were classified into two diagnostic categories: PD-Cognitive Unimpaired (CU) ( n  = 171) and PD-MCI ( n  = 104). NA was applied to construct Gaussian Graphical Models for each diagnostic group, where nodes represent cognitive tests and demographic factors, and edges represent their interconnections. The NA revealed substantial differences between the cognitive networks of PD-CU and PD-MCI patients. Specifically, the network of PD-MCI patients appears less sparse, with some weakened relationships between nodes. Overall, the results support the presence of a cognitive reorganization in PD-MCI patients, potentially indicating a functional compensation mechanism. In conclusion, this study enhances the understanding of the cognitive mechanisms underlying cognitive decline in patients with PD.
When Sex Overcomes Motor Phenotype: New Evidence on Cognitive and Neurobehavioral Symptoms in Parkinson's Disease
Background Sex‐based differences in cognitive and behavioral symptoms have been previously reported in Parkinson's disease (PD), as well as the effects of motor lateralization and phenotypes at onset. However, no studies investigated the interaction between these variables. Objective We aimed to evaluate whether sex differences interact with motor phenotype and lateralization at the onset of cognitive and neurobehavioral symptoms. Methods: Data from 304 PD patients (119 women and 185 men) were retrospectively examined, including comprehensive neurologic, neuropsychological, and neurobehavioral assessments. MANCOVAs on tests divided based on the results of a principal component analysis were performed to compare cognitive and behavioral performance, considering sex, motor phenotype at onset, and onset lateralization as grouping variables. Analyses were also performed on a subsample of patients (n = 200) in which subgroups were balanced in terms of motor and demographic features. Results: Significant sex effects were found, with females showing higher performance compared to males in verbal long‐term memory (p = 0.00003), social cognition (p = 0.0001), and naming tasks (p = 0.03009). Significant interactions between motor phenotype and sex were found: rigid‐akinetic (RA) females showed higher performance than other groups in a verbal memory task (p = 0.0183), and tremor‐dominant (TD) females made more errors than the other groups in an inhibitory control task (p = 0.03853). Interestingly, RA females performed better on verbal learning than tremor‐dominant (TD) males (p = 0.00911), suggesting that sex effects overcome motor phenotype in this cognitive function. No significant interactions were found between sex and lateralization at onset concerning cognitive variables. However, patients with right‐sided onset, in particular females, self‐reported higher levels of behavioral symptoms. Conclusions: These results emphasize the complex relationship between demographic and PD motor features in delineating the clinical phenotype, which should be considered in designing patient‐tailored strategies for disease monitoring and intervention. Patients with Parkinson's disease (PD) show variability in clinical manifestations, with symptoms depending on sex, type, and their lateralization at onset (motor phenotype and lateralization). While these factors have been investigated individually, their interaction has not. Therefore, the aim of our study was to verify how sex differences interact with motor features to affect non‐motor symptoms. To do this, we collected data from 304 patients (119 women and 185 men), who underwent assessment of motor symptoms, cognitive abilities, and mood disturbances. Statistical analyses were performed on cognitive and behavioral performance, considering sex, motor phenotype, and lateralization at onset as grouping variables. We found significant sex differences across multiple cognitive domains: women outperformed men in verbal memory and naming and emotion recognition, while men performed better in visuospatial tasks. In addition, women reported higher levels of depression and anxiety than men. We also found a significant interaction between sex and motor phenotype: females with rigidity at onset (RA onset) showed better performance than other groups in a verbal memory task. Interestingly, this group outperformed males with tremor at onset (TD onset) in verbal memory, suggesting that sex may have a stronger influence than motor phenotype in this cognitive area. Sex and motor phenotype also interact in an inhibitory control task, where TD females made more errors. Right‐side onset—in particular in women—was associated with more depression symptoms compared to the other groups. Overall, these findings show that sex interacts in a complex way with onset motor features. This aspect should be considered for patient‐tailored treatment strategies.
When Size Matters: New Insights on How Seed Size Can Contribute to the Early Stages of Plant Development
The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterward spread on land. In particular, seed size had a pivotal role in evolutionary success and agronomic traits, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size and how they influence seed germination. Moreover, new insights on the genetic–molecular control of this adaptive trait are presented.
The DOF Transcription Factors in Seed and Seedling Development
The DOF (DNA binding with one finger) family of plant-specific transcription factors (TF) was first identified in maize in 1995. Since then, DOF proteins have been shown to be present in the whole plant kingdom, including the unicellular alga Chlamydomonas reinhardtii. The DOF TF family is characterised by a highly conserved DNA binding domain (DOF domain), consisting of a CX2C-X21-CX2C motif, which is able to form a zinc finger structure. Early in the study of DOF proteins, their relevance for seed biology became clear. Indeed, the PROLAMIN BINDING FACTOR (PBF), one of the first DOF proteins characterised, controls the endosperm-specific expression of the zein genes in maize. Subsequently, several DOF proteins from both monocots and dicots have been shown to be primarily involved in seed development, dormancy and germination, as well as in seedling development and other light-mediated processes. In the last two decades, the molecular network underlying these processes have been outlined, and the main molecular players and their interactions have been identified. In this review, we will focus on the DOF TFs involved in these molecular networks, and on their interaction with other proteins.
Cognitive Outcomes of Advanced Therapies in Parkinson's Disease: A Systematic Review of Apomorphine and Levodopa–Carbidopa Intestinal Gel Therapies
Background Parkinson's disease (PD) treatments, such as apomorphine (APO) and levodopa–carbidopa intestinal gel (LCIG), represent advanced therapeutic options for managing motor symptoms. However, clear selection criteria and well‐defined cognitive outcomes are lacking. This systematic review specifically aimed to address these gaps by assessing the cognitive impact of APO and LCIG in PD patients. Methods A systematic review was conducted following PRISMA guidelines, with searches in PubMed, Web of Science, Scopus, and Embase. Two authors screened studies based on key inclusion criteria, including at least two cognitive tests, and a follow‐up of 6 months or more. The risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS). Results Fifteen studies were identified (7 APO and 8 LCIG). APO generally preserved cognitive function over a 12‐month follow‐up, with some decreases in visuospatial memory and executive functions. LCIG, with a 28‐month follow‐up, showed more extensive cognitive decline, particularly in patients with pre‐existing impairments. Variability in cognitive tests made direct comparisons difficult. Discussion APO may have a more favorable cognitive profile than LCIG. However, differences in follow‐up duration, moderate risk of bias, and inconsistent cognitive assessments warrant cautious interpretation. Improved patient selection and comprehensive cognitive evaluations are recommended for future practice.
Osteomyelitis of the Lower Limb: Diagnostic Accuracy of Dual-Energy CT versus MRI
Background: MRI is the preferred imaging technique for the identification of osteomyelitis. The key element for diagnosis is the presence of bone marrow edema (BME). Dual-energy CT (DECT) is an alternative tool which is able to identify BME in the lower limb. Purpose: To compare the diagnostic performance of DECT and MRI for osteomyelitis, using clinical, microbiological, and imaging data as reference standards. Materials and Methods: This prospective single-center study enrolled consecutive patients with suspected bone infections undergoing DECT and MRI imaging from December 2020 to June 2022. Four blinded radiologists with various experience levels (range of 3-21 years) evaluated the imaging findings. Osteomyelitis was diagnosed in the presence of BMEs, abscesses, sinus tracts, bone reabsorption, or gaseous elements. The sensitivity, specificity, and AUC values of each method were determined and compared using a multi-reader multi-case analysis. A p value < 0.05 was considered significant. Results: In total, 44 study participants (mean age 62.5 years ± 16.5 [SD], 32 men) were evaluated. Osteomyelitis was diagnosed in 32 participants. For the MRI, the mean sensitivity and specificity were 89.1% and 87.5%, while for the DECT they were 89.0% and 72.9%, respectively. The DECT demonstrated a good diagnostic performance (AUC = 0.88), compared with the MRI (AUC = 0.92) (p = 0.12). When considering each imaging finding alone, the best accuracy was achieved by considering BME (AUC for DECT 0.85 versus AUC of MRI of 0.93, with p = 0.07), followed by the presence of bone erosions (AUC 0.77 for DECT and 0.53 for MRI, with p = 0.02). The inter-reader agreement of the DECT (k = 88) was similar to that of the MRI (k = 90). Conclusion: Dual-energy CT demonstrated a good diagnostic performance in detecting osteomyelitis.
Ultrasound-Guided Percutaneous Bone Biopsy: Feasibility, Diagnostic Yield and Technical Notes
While nowadays, CT-guided bone biopsy represents the gold standard tool for histopathological and microbiological diagnosis of skeletal lesions, the role of US-guided bone biopsy has not yet been fully explored. US-guided biopsy offers several advantages, such as the absence of ionizing radiation, fast acquisition time, as well as good intra-lesional echo, and structural and vascular characterization. Despite that, a consensus in regard to its applications in bone neoplasms has not been established. Indeed CT-guided technique (or fluoroscopic ones) still represents the standard choice in clinical practice. This review article aims to review the literature data about US-guided bone biopsy, underlying clinical-radiological indications, advantages of the procedure and future perspectives. Bone lesions taking the best advantages of the US-guided biopsy are osteolytic, determining the erosion of the overlying bone cortex and/or with an extraosseous soft-tissue component. Indeed, osteolytic lesions with extra-skeletal soft-tissue involvement represent a clear indication for US-guided biopsy. Moreover, even lytic bone lesions with cortical thinning and/or cortical disruption, especially located in the extremities or pelvis, can be safely sampled with US guidance with very good diagnostic yield. US-guided bone biopsy is proven to be fast, effective and safe. Additionally, it offers real-time needle evaluation, an advantage when compared to CT-guided bone biopsy. In the current clinical settings, it seems relevant to select the exact eligibility criteria for this imaging guidance since the effectiveness can vary depending on the type of lesion and body site involved.
Failure of anti Interleukin-1 β monoclonal antibody in the treatment of recurrent pericarditis in two children
Background Recurrent pericarditis (RP) is a complication (15–30%) of acute pericarditis with an unknown etiology. Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, with the addition of corticosteroids in resistant or intolerant cases. In the last decade anakinra was shown as an effective treatment in patients with colchicine resistant and steroid-dependent RP, initially in anecdotal reports in children and more recently in a randomized trial. Canakinumab is a monoclonal antibody selectively blocking IL-1β and its use is only anecdotally reported to treat pericarditis. We report two pediatric patients with refractory recurrent pericarditis, who presented an optimal response to anakinra treatment but prompt relapse after switch to canakinumab. Case presentation The first patient is a girl with Recurrent Pericarditis started in April 2015, after heart surgery. NSAIDs and oral steroids were started, with prompt relapse after steroid suspension. The child showed a steroid-dependent RP; anakinra was therefore started with excellent response, but discontinued after 2 weeks for local reactions. In July 2016 therapy with canakinumab was started. She experienced four relapses during canakinumab therapy despite dosage increase and steroid treatment. In January 2018 a procedure of desensitization from anakinra was performed, successfully. Anakinra as monotherapy is currently ongoing, without any sign of flare. The second patient is a girl with an idiopathic RP, who showed an initial benefit from NSAIDs and colchicine. However, 10 days after the first episode a relapse occurred and therapy with anakinra was established. Two months later, while being in complete remission, anakinra was replaced with canakinumab due to patient’s poor compliance to daily injections. She experienced a relapse requiring steroids 10 days after the first canakinumab injection. Anakinra was subsequently re-started with complete remission, persisting after 24 months follow-up. Conclusions We describe two cases of failure of the treatment with anti-IL-1β monoclonal antibodies in steroid- dependent idiopathic RP. This anecdotal and preliminary observation suggests a different efficacy of the two IL-1 blockers in the management of RP and support a possible pivotal role of IL-1α in the pathogenesis of this condition.
Inhibition of Polycomb Repressive Complex 2 activity reduces trimethylation of H3K27 and affects development in Arabidopsis seedlings
Background Polycomb repressive complex 2 (PRC2) is an epigenetic transcriptional repression system, whose catalytic subunit (ENHANCER OF ZESTE HOMOLOG 2, EZH2 in animals) is responsible for trimethylating histone H3 at lysine 27 (H3K27me3). In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. Results We show here that the 1,5-bis (3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one compound (RDS 3434), previously reported as an EZH2 inhibitor in human leukemia cells, is active on the Arabidopsis catalytic subunit of PRC2, since treatment with the drug reduces the total amount of H3K27me3 in a dose-dependent fashion. Consistently, we show that the expression level of two PRC2 targets is significantly increased following treatment with the RDS 3434 compound. Finally, we show that impairment of H3K27 trimethylation in Arabidopsis seeds and seedlings affects both seed germination and root growth. Conclusions Our results provide a useful tool for the plant community in investigating how PRC2 affects transcriptional control in plant development.
The value of high-resolution computed tomography (HRCT) to determine exercise ventilatory inefficiency and dynamic hyperinflation in adult patients with cystic fibrosis
Introduction In Cystic Fibrosis (CF), exercise ventilatory inefficiency and dynamic hyperinflation (DH) cause exercise limitation and induce poor exercise tolerance. High-resolution computed tomography (HRCT) of the lung can detect pulmonary abnormalities in CF patients. We aimed to identify the determinants of exercise ventilatory inefficiency and DH using HRCT-derived metrics. Methods Fifty-two adult CF patients were prospectively enrolled; all participants underwent cardio-pulmonary exercise test (CPET) and HRCT. Radiological impairment was evaluated by the Brody II scoring system. Slope and intercept of the minute ventilation/CO 2 production (V’ E /V’ CO2 ) regression line and the ratio of inspiratory capacity/total lung capacity (IC/TLC) at rest and at peak of exercise were measured. Results Four groups of patients were identified based on the combination of ventilatory efficiency ( Vef ) or inefficiency ( Vin ) and the presence/absence of DH. Compared to other groups, CF adults with Vin and DH had worse functional status and higher total (T), bronchiectasis (B) and air trapping (AT) scores at HRCT. Significant correlations were found between V’ E /V’ CO2 intercept and V’ E /V’ CO2 slope (ρ − 0.455, p  = 0.001) and between V’ E /V’ CO2 intercept and Δ inspiratory capacity (IC) (ρ − 0.334, p  = 0.015 ). Regression analysis identified AT score (cut-off 7.9, odds ratio-OR 3.50) as the only independent predictor of V in and T (cut-off 53.6, OR 4.98), B (cut-off 16.1, OR 4.88), airways wall thickening (AWT) (cut-off 13, OR 3.41), and mucous plugging (MP) scores (cut-off 11.7, OR 4.18) as significant predictors of DH. Conclusion In adult CF cohort, values of HRCT metrics are determinants of Vin (AT) and DH (T, B, AWT, MP).