Simultaneous EEG-fMRI in Patients with Unverricht-Lundborg Disease: Event-Related Desynchronization/Synchronization and Hemodynamic Response Analysis

We performed simultaneous acquisition of EEG-fMRI in seven patients with Unverricht-Lundborg disease (ULD) and in six healthy controls using self-paced finger extension as a motor task. The event-related desynchronization/synchronization (ERD/ERS) analysis showed a greater and more diffuse alpha desynchronization in central regions and a strongly reduced post-movement beta-ERS in patients compared with controls, suggesting a significant dysfunction of the mechanisms regulating active movement and movement end. The event-related hemodynamic response obtained from fMRI showed delayed BOLD peak latency in the contralateral primary motor area suggesting a less efficient activity of the neuronal populations driving fine movements, which are specifically impaired in ULD

Grasping the semantic of actions: a combined behavioral and MEG study

There is experimental evidence that the brain systems involved in action execution also play a role in action observation and understanding. Recently, it has been suggested that the sensorimotor system is also involved in language processing. Supporting results are slower response times and weaker motor-related MEG Beta band power suppression in semantic decision tasks on single action verbs labels when the stimulus and the motor response involve the same effector. Attenuated power suppression indicates decreased cortical excitability and consequent decreased readiness to act. The embodied approach forwards that the simultaneous involvement of the sensorimotor system in the processing of the linguistic content and in the planning of the response determines this language-motor interference effect. Here, in a combined behavioral and MEG study we investigated to what extent the processing of actions visually presented (i.e., pictures of actions) and verbally described (i.e., verbs in written words) share common neural mechanisms. The findings demonstrated that, whether an action is experienced visually or verbally, its processing engages the sensorimotor system in a comparable way. These results provide further support to the embodied view of semantic processing, suggesting that this process is independent from the modality of presentation of the stimulus, including language

BRAF and MLH1 Analysis Algorithm for the Evaluation of Lynch Syndrome Risk in Colorectal Carcinoma Patients: Evidence-Based Data from the Analysis of 100 Consecutive Cases

settingsOrder Article Reprints Open AccessFeature PaperArticle BRAF and MLH1 Analysis Algorithm for the Evaluation of Lynch Syndrome Risk in Colorectal Carcinoma Patients: Evidence-Based Data from the Analysis of 100 Consecutive Cases by Thais Maloberti 1,2,†ORCID,Antonio De Leo 1,2,†ORCID,Viviana Sanza 2,Lidia Merlo 2,Michela Visani 1ORCID,Giorgia Acquaviva 1,Sara Coluccelli 1,2ORCID,Annalisa Altimari 2,3,Elisa Gruppioni 2,3,Stefano Zagnoni 2,3,Daniela Turchetti 4,Sara Miccoli 4,Michelangelo Fiorentino 5,6ORCID,Antonietta D’Errico 3ORCID,Dario de Biase 7,*,‡ORCID andGiovanni Tallini 1,2,‡ORCID 1 Department of Experimental, Diagnostic and Specialty Medicine, Anatomic Pathology Unit-University of Bologna Medical Center, 40138 Bologna, Italy 2 Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 3 Department of Pathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 4 Unit of Medical Genetics, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 5 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy 6 Pathology Department, Maggiore Hospital, 40133 Bologna, Italy 7 Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy * Author to whom correspondence should be addressed. † These authors contributed equally to this work. ‡ These authors contributed equally to this work. J. Mol. Pathol. 2022, 3(3), 115-124; https://doi.org/10.3390/jmp3030011 Received: 30 March 2022 / Revised: 27 May 2022 / Accepted: 21 June 2022 / Published: 25 June 2022 (This article belongs to the Collection Feature Papers in Journal of Molecular Pathology) Download Browse Figures Versions Notes Abstract Several causes may lead to CRC, either extrinsic (sporadic forms) or genetic (hereditary forms), such as Lynch syndrome (LS). Most sporadic deficient mismatch repair (dMMR) CRC cases are characterized by the methylation of the MLH1 promoter gene and/or BRAF gene mutations. Usually, the first test performed is the mismatch repair deficiency analysis. If a tumor shows a dMMR, BRAF mutations and then the MLH1 promoter methylation status have to be assessed, according to the ACG/ASCO screening algorithm. In this study, 100 consecutive formalin-fixed and paraffin-embedded samples of dMMR CRC were analyzed for both BRAF mutations and MLH1 promoter methylation. A total of 47 (47%) samples were BRAF p.V600E mutated, while MLH1 promoter methylation was found in 77 cases (77.0%). The pipeline “BRAF-followed-by-MLH1-analysis” led to a total of 153 tests, while the sequence “MLH1-followed-by-BRAF-analysis” resulted in a total of 123 tests. This study highlights the importance of performing MLH1 analysis in LS screening of BRAF-WT specimens before addressing patients to genetic counseling. We show that MLH1 analysis performs better as a first-line test in the screening of patients with LS risk than first-line BRAF analysis. Our data indicate that analyzing MLH1 methylation as a first-line test is more cost-effective

Multi-Gene Next-Generation Sequencing Panel for Analysis of BRCA1/BRCA2 and Homologous Recombination Repair Genes Alterations Metastatic Castration-Resistant Prostate Cancer

: Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the BRCA1/BRCA2 genes, as well as in the homologous recombination repair (HRR) genes. A total of 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel evaluating a total of 1360 amplicons in 24 HRR genes. Of the 50 cases, 23 specimens (46.0%) had an mCRPC harboring a pathogenic variant or a variant of uncertain significance (VUS), whereas in 27 mCRPCs (54.0%), no mutations were detected (wild-type tumors). BRCA2 was the most commonly mutated gene (14.0% of samples), followed by ATM (12.0%), and BRCA1 (6.0%). In conclusion, we have set up an NGS multi-gene panel that is capable of analyzing BRCA1/BRCA2 and HRR alterations in mCRPC. Moreover, our clinical algorithm is currently being used in clinical practice for the management of patients with mCRPC

Non-Functional Jaw Muscular Activity in Patients with Disorders of Consciousness Revealed by A Long-Lasting Polygraphy

The presence of involuntary, non-functional jaw muscle activity (NFJMA) has not yet been assessed in patients with disorders of consciousness (DOC), although the presence of bruxism and other forms of movement disorders involving facial muscles is probably more frequent than believed. In this work, we evaluated twenty-two prolonged or chronic DOC patients with a long-lasting polygraphic recording to verify NFJMA occurrence and assess its neurophysiological patterns in this group of patients. A total of 5 out of 22 patients showed the presence of significant NFJMA with electromyographic patterns similar to what can be observed in non-DOC patients with bruxism, thus suggesting a disinhibition of masticatory motor nuclei from the cortical control. On the other hand, in two DOC patients, electromyographic patterns advised for the presence of myorhythmia, thus suggesting a brainstem/diencephalic involvement. Functional, non-invasive tools such as long-lasting polygraphic recordings should be extended to a larger sample of patients, since they are increasingly important in revealing disorders potentially severe and impacting the quality of life of DOC patients

Ultrastructural detection of environmental nanoparticles in circulating blood

The increase in the incidence of acute myeloid leukemia (AML) may suggest a possible environmental etiology. PM2.5 was declared by the International Agency for Research on Cancer (WHO organ) a Class I carcinogen. To date, no reports have focused on particulate environmental pollution together with AML. The study investigated the presence and composition of particulate matter in circulating blood with a Environmental Scanning Electron Microscope coupled with an Energy Dispersive Spectroscope for the elemental analysis of the samples. 38 peripheral blood samples, 19 AML cases and 19 healthy controls, were analysed. A significant overload of particulate matter-derived nanoparticles linked or aggregated to blood components was found in AML patients, while almost absent in matched healthy controls. Two tailed Student’s t-test, MANOVA and Principal Component Analysis indicated that the total numbers of aggregates and particles were statistically different between cases and controls (MANOVA,

Benda-BEAM High-Dose Therapy Prior to Auto-SCT is Effective in Resistant/Relapsed DLBCL

Abstract Background: The most important drawback of clinical trials of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) in lymphomas is the high heterogeneity of histological entities. Therefore, the statistical power is reduced, and data are not conclusive. We previously demonstrated the safety of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (BeEAM) prior to ASCT in resistant/relapsed lymphoma patients. This combination of drugs was able to induce a high CR rate in a population that did not have an opportunity of being cured with other therapies. However, that study enrolled both Hodgkin and non-Hodgkin lymphoma patients. Aims: We designed a phase II study to evaluate the efficacy of the BeEAM conditioning in resistant/relapsed diffuse large B-cell non-Hodgkin lymphoma (DLBCL) patients. Patients and methods: The study was registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2011-001246-14. Until now, 61 patients (median age 54 years, range 19-69) with resistant/relapsed DLBCL were enrolled. The primary end-point of the study is to evaluate the 1-year complete remission rate. Results: Briefly, 46/61 patients had advanced stage disease (III-IV); 20 were primary refractory and 41 had relapsed after a median number of 2 lines of therapy (range: 1-3). Twenty-one patients had 1 or more relevant comorbidities (range: 1- 5). 30 patients were in II or subsequent CR after salvage therapy, whereas 27 were in PR and 4 had stable or progressive disease. A median number of 5.72x106 CD34+/kg cells (range 2.21-10.60) collected from peripheral blood was reinfused to patients. All patients engrafted, with a median time to ANC>0.5x109/l of 10 days. Median times to achieve a platelet count >20x109/l and >50x109/l were 12 and 17 days respectively. Twenty-two out of 61 patients presented a fever of unknown origin (36%), whereas 24 patients (39%) presented a clinically documented infection. All patients received G-CSF after transplant for a median time of 8 days (range: 8-13). One patient died due to an incomplete hematological recovery after transplant, producing an overall transplant related mortality of 2.7%. Fifty-seven patients are evaluable for response: 48/57 (84%) obtained a CR, 3/57 (5%) a PR, whereas 6/57 (11%) did not respond to therapy. After a median follow-up of 10.5 months after transplant (range 3-37), 6/57 (11%) patients were refractory, 12/57 (21%) relapsed and 39/57 (68%) are still alive, in continuous CR. Conclusion: Our clinical trial was designed to closely resemble real-world treatment for these patients. During the study, we transplanted a similar proportion of the patients that would have received ASCT in a real-world scenario. While we cannot make sound comparisons without head-to-head trials, results from previous studies using HDT regimens in DLCBL have not been as encouraging as ours. Accordingly, our data preliminary provide the evidence that the Benda-BEAM regimen is safe and has promising high efficacy in resistant-relapsed aggressive DLBCL patients. Acknowledgments: The study was supported in part by AIL Pesaro Onlus. Mundipharma Italy is grateful acknowledged for providing Bendamustine free of charge. Disclosures Patriarca: Janssen-Cilag, Celgene, Merck Sharp & Dohme: Honoraria. Zinzani:Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees

Gender Differences in Psychological Well-Being and Distress During Adolescence

Differences between boys and girls have been found in terms of psychological well-being and distress. Girls report lower level of psychological well-being and higher psychological distress

Higher order spectral analysis of scalp EEG activity reveals non-linear behavior during rhythmic visual stimulation

Objective. Flickering visual stimulation is known to evoke rhythmic oscillations in the electroencephalographic (EEG) activity, called steady-state visually evoked potentials (SSVEP). The presence of harmonic components in the EEG signals during SSVEP suggests the non-linearity of the visual-system response to rhythmic stimulation, but the nature of this behavior has not been deeply understood. The aim of this study is the quantitative evaluation and characterization of this non-linear phenomenon and its interference with the physiological alpha rhythm by means of spectral and higher order spectral analysis. Approach. EEG signals were acquired in a group of 12 healthy subjects during a pattern-reversal stimulation protocol at three different driving frequencies (7.5 Hz, 15 Hz and 24 Hz). Spectral power values were estimated, after Laplacian spatial filtering, to quantitatively evaluate the changes in the power of the individual alpha and stimulation frequencies related harmonic components. Bicoherence measure were employed to assess the presence of quadratic phase coupling (QPC) at each channel location. Main results. Our analysis confirmed a strong non-linear response to the rhythmic stimulus principally over the parieto-occipital channel locations and a simultaneous significant alpha power suppression during 7.5 Hz and 15 Hz stimulation. A prominent sub-harmonic component characterized the resonance behavior of the 24 Hz stimulation. Significance. The findings presented suggest that bicoherence is a useful tool for the identification of QPC interactions between stimulus-related frequency components within the same signal and the characterization of the non-linearity of SSVEP-induced harmonics generation. In addition, the applied methodology demonstrates the presence of coupled EEG rhythms (harmonics of the main oscillation) both in resting condition and during stimulation, with different characteristics in the distinct brain areas