Ultrastructural Characterization of PBMCs and Extracellular Vesicles in Multiple Sclerosis: A Pilot Study.

Growing evidence identifies extracellular vesicles (EVs) as important cell-to-cell signal transducers in autoimmune disorders, including multiple sclerosis (MS). If the etiology of MS still remains unknown, its molecular physiology has been well studied, indicating peripheral blood mononuclear cells (PBMCs) as the main pathologically relevant contributors to the disease and to neuroinflammation. Recently, several studies have suggested the involvement of EVs as key mediators of neuroimmune crosstalk in central nervous system (CNS) autoimmunity.

Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.

Background: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment.

Multi-Criterial Model for Weighting Biological Risk Factors in Multiple Sclerosis: Clinical and Health Insurance Implications.

The etiology of Multiple Sclerosis (MS) remains undetermined. Its pathogenic risk factors are thought to play a negligible role individually in the development of the disease, instead assuming a pathogenic role when they interact with each other. Unfortunately, the statistical weighting of this pathogenic role in predicting MS risk is currently elusive, preventing clinical and health insurance applications.

Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens.

Adoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding of T-cell responses to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated the ability of patient-derived tumor organoids (PDTO) to fulfill this need and evaluated their utility as a tool for selecting T-cells for adoptive cell therapy.

Poly(ADP-ribose)-binding protein RCD1 is a plant PARylation reader regulated by Photoregulatory Protein Kinases.

Poly(ADP-ribosyl)ation (PARylation) is a reversible post-translational protein modification that has profound regulatory functions in metabolism, development and immunity, and is conserved throughout the eukaryotic lineage. Contrary to metazoa, many components and mechanistic details of PARylation have remained unidentified in plants. Here we present the transcriptional co-regulator RADICAL-INDUCED CELL DEATH1 (RCD1) as a plant PAR-reader.

Fluphenazine-Induced Neurotoxicity with Acute Almost Transient Parkinsonism and Permanent Memory Loss: Lessons from a Case Report.

We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven months. Unlike gradual drug-induced parkinsonism, our patient experienced acute extrapyramidal syndrome (EPS), reaching significant motor and sphincter disability in just a few days, followed by a gradual incomplete recovery over more than six months. In fact, after drug discontinuation, hypomimia and slight left hemi-somatic rigidity with bradykinesia remained, as well as stable non-progressive memory disturbances.

Changes in Brain Volumes Are Relevant during Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: Lessons from a Case Report.

This is a case report concerning a Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) with cerebellar localization and wakefulness disturbances. Awakening and clinical improvement dramatically occurred as soon as the immune reconstitution inflammatory syndrome (IRIS) took place, being it mild in nature and colocalizing with the PML lesion. In these ideal experimental conditions, we applied brain magnetic resonance imaging post-analysis in order to know changes in brain volumes underlying the pathological process over the infection period.

Dementia-Associated Compulsive Singing (DACS): Presentation of Unpublished Clinical Cases Miniseries.

Dementia-associated compulsive singing (DACS) is a neurotransmettitorial-based behavioral disturbance, characterized by an unabating melodic expression, occurring in patients that suffer from evolved dementia. Previously described only as a "punding" aspect of the dopamine dysregulation syndrome (DDS) in the Parkinson's disease (PD), compulsive singing has now been described, for the first time, in four non-PD patients effectively treated with Haloperidol or Quetiapine. Unlike the DDS-associated conditions, in our cases DACS is not pharmacologically induced, being that all patients were L-dopa-free.

The superior salinity tolerance of bread wheat cultivar Shanrong No. 3 is unlikely to be caused by elevated Ta-sro1 poly-(ADP-ribose) polymerase activity.

Structural and biochemical analyses demonstrate that the elevated salinity tolerance of bread wheat cultivar Shanrong No. 3 is unlikely to be caused by elevated Ta-sro1 poly(ADP-ribose) polymerase activity.

GANAB and -Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review.

Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident -glycans participate with the GlcManGlcNAc highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio.

Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor-Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors.

Adoptive cellular therapy (ACT) targeting neoantigens can achieve durable clinical responses in patients with cancer. Most neoantigens arise from patient-specific mutations, requiring highly individualized treatments. To broaden the applicability of ACT targeting neoantigens, we focused on TP53 mutations commonly shared across different cancer types.

Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers.

The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering of cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures of CD8 and CD4 neoantigen-reactive tumor-infiltrating lymphocytes (TILs). Neoantigen-specific TILs exhibited tumor-specific expansion with dysfunctional phenotypes, distinct from blood-emigrant bystanders and regulatory TILs.

Experimental Evaluation of the Mechanical Strengths and the Thermal Conductivity of GGBFS and Silica Fume Based Alkali-Activated Concrete.

Alkali-activated concrete (AAC) could be a solution to use a cement-less binder and recycled materials for producing concrete reducing the carbon dioxide emission and the demand for raw materials, respectively. In addition to the environmental aspect, AACs can achieve mechanical characteristics higher than those of ordinary Portland concrete (OPC) but also an improvement of the thermal insulation capacity. Despite the positive results available in the scientific literature, the use of AACs in construction practice is still limited mainly due to the absence of codification for the mix design and consequently of specific design rules.

IFP35 Is a Relevant Factor in Innate Immunity, Multiple Sclerosis, and Other Chronic Inflammatory Diseases: A Review.

Discovered in 1993 by Bange et al., the 35-kDa interferon-induced protein (IFP35) is a highly conserved cytosolic interferon-induced leucine zipper protein with a 17q12-21 coding gene and unknown function. Belonging to interferon stimulated genes (ISG), the IFP35 reflects the type I interferon (IFN) activity induced through the JAK-STAT phosphorylation, and it can homodimerize with N-myc-interactor (NMI) and basic leucine zipper transcription factor (BATF), resulting in nuclear translocation and a functional expression.

GANAB as a Novel Biomarker in Multiple Sclerosis: Correlation with Neuroinflammation and IFI35.

Multiple sclerosis (MS) still lacks reliable biomarkers of neuroinflammation predictive for disease activity and treatment response. Thus, in a prospective study we assessed 55 MS patients (28 interferon (IFN)-treated, 10 treated with no-IFN therapies, 17 untreated) and 20 matched healthy controls (HCs) for the putative correlation of the densitometric expression of glucosidase II alpha subunit (GANAB) with clinical/paraclinical parameters and with interferon-induced protein 35 (IFI35). We also assessed the disease progression in terms of the Rio Score (RS) in order to distinguish the responder patients to IFN therapy (RS = 0) from the non-responder ones (RS ≥ 1).

Assessment of Mechanical and Thermal Properties of Hemp-Lime Mortar.

The use of renewable and natural materials characterized by the low environmental impact is nowadays a key issue for the sustainable development of the construction industry. For this reason, the interest for natural fibers, to be used as reinforcement in composites as an alternative to other fibers, is continuously growing. In this paper, the use of hemp for reinforcing lime mortar used as plaster is considered with a multidisciplinary approach, taking into consideration the structural and thermal performance.

Early-Life Exposure to Environmental Air Pollution and Autism Spectrum Disorder: A Review of Available Evidence.

The number of children diagnosed with Autism Spectrum Disorder (ASD) has rapidly increased globally. Genetic and environmental factors both contribute to the development of ASD. Several studies showed linkage between prenatal, early postnatal air pollution exposure and the risk of developing ASD.

Objective evaluation and predictive value of olfactory dysfunction among patients hospitalized with COVID-19.

Objectives: Olfactory dysfunction is a frequent feature of COVID-19. Despite the growing evidence, current knowledge on the subject remains insufficient, so that data obtained with different tools, from multiple centers and in distinct scenarios are welcome. Yet, the predictive value of olfactory dysfunction in terms of the overall prognosis of COVID-19 is unknown.

The Age-Related Efficacy of Dimethyl Fumarate and Natalizumab in the Real-World Management of Multiple Sclerosis.

We investigated the comparative age-related efficacy of dimethyl fumarate (DMF) and natalizumab (NTZ) in clinical practice on multiple sclerosis (MS). Research in this area is lacking in the previous literature. In a three-year retrospective and clinical-paraclinical study, we compared 173 DMF patients and 94 NTZ patients with a similar average age (40 years) and disease duration (DD) (10 years).

The influence of lifestyle factors on miRNA expression and signal pathways: a review.

The term 'lifestyle' includes different factors that contribute to the maintenance of a good health status. Increasing evidences suggest that lifestyle factors may influence epigenetic mechanisms, such as miRNAs expression. The dysregulation of miRNAs can modify the expression of genes and molecular pathways that may lead to functional alterations.

Olfactory function and findings on chest computed tomography in COVID-19: is there any correlation?

Background: Olfactory dysfunction is frequent in COVID-19 and it might occur along with pulmonary involvement. These manifestations do not seem to share pathophysiological mechanisms, but clinical data on the subject is lacking. Aims/Objectives: This study aims to correlate the olfactory function (OF) and the radiological pulmonary involvement among in-hospital patients with COVID-19.

The design of safe classrooms of educational buildings for facing contagions and transmission of diseases: A novel approach combining audits, calibrated energy models, building performance (BPS) and computational fluid dynamic (CFD) simulations.

The proposed investigation is aimed at providing useful suggestions and guidelines for the renovation of educational buildings, in order to do University classrooms safe and sustainable indoor places, with respect to the 2020 SARS-CoV-2 global pandemic. Classrooms and common spaces have to be thought again, for a new "in-presence" life, after the recent worldwide emergency following the spring 2020 pandemic diffusion of COVID-19. In this paper, starting from a real case study, and thus the architectural and technological refurbishment of an Italian University building (Campobasso, South Italy, cold climate), with the aims of improving the classrooms' quality and safety, a comprehensive approach for the retrofit design is proposed.

IFI35 as a biomolecular marker of neuroinflammation and treatment response in multiple sclerosis.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with unpredictable clinical outcome. As such, there is an urgent need to identify biomarkers that can predict the treatment response. Therefore, in an open-label, clinical, paraclinical and molecular prospective study, we assessed 50 interferon (IFN) treated MS patients for Rio Score (RS)/Modified Rio Score (MRS) and densitometric expression of the interferon-induced protein 35 (IFI35), a signal-protein with potential to be clinically relevant in the management of the disease.