Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

Photodegradation of Bamboo: A Study on Changes in Mechanical Performances

One of the main concerns in using natural materials in construction, such as bamboo, regards their durability. Ultra violet (UV)irradiation is claimed as a damaging agent; therefore, it is important to study its effect. Several studies have shown that bamboo components such as lignin are subjected to photochemical degradation, but it is not well understood how this affects the mechanical properties of bamboo. The aim of this paper is to explore the correlation between photodegradation and bamboo mechanical performance. Bamboo samples were exposed to accelerated UV ageing for different times (from 6 to 360 h) and then subjected to a four-point bending test. Since one of the ways to stabilize bamboo is to thermally treat it, the tests were conducted on natural untreated bamboo and treated bamboo with a traditional flame treatment. Modifications of the chemical features of the material were analyzed with Fourier Trasform Infra Red (FTIR) spectroscopy, while modifications of the morphological features were analyzed byEnvironmental Scanning Electron Microscopy ESEM and optical microscopy observations. The results show that the bending behavior of bamboo is not compromised by UV exposure up to 360 h. In fact, although a progressive degradation of lignin is reported and cracks in the fiber walls are highlighted from micrographs, no effects were found on the fiber length.     

Modelling Strategies for Reinforced Concrete Elements under Corrosion Degradation

Aging and corrosion of reinforced concrete structures (RCS) is becoming a global problem, thus proper procedures for simulating the structural performance of corroded RCS should be assessed. Among the main corrosion effects, concrete cover cracking and reinforcement cross-section reduction may influence the materials’ constitutive laws, moreover the confinement contribution and the lateral instability of the longitudinal rebars can be modified. In the present paper, the predictive models available in the scientific literature to assess the materials’ mechanical properties of corroded RCS are recalled and employed into a novel model to derive the theoretical moment–curvature relationships for the cross-section of square and rectangular corroded reinforced concrete elements. The model accounts for cover spalling, buckling of longitudinal reinforcing bars, reduction in confinement pressures, reduction in concrete constitutive law due to the concrete cracking induced by rust formation and decay of mechanical properties for corroded reinforcements. The obtained results are compared with the classical simplified models for corroded RCS, highlighting that buckling and confinement variations cannot be disregarded into a reliable modelling strategy, especially when local ductility plays a key role in the performed investigations.     

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.     

Liquid Biopsy at Home: Delivering Precision Medicine for Patients with Cancer During the COVID-19 Pandemic

CoronaVirus disease-2019 has changed the delivery of health care worldwide and the pandemic has challenged oncologists to reorganize cancer care. Recently, progress has been made in the field of precision medicine to provide to patients with cancer the best therapeutic choice for their individual needs. In this context, the Foundation Medicine (FMI)-Liquid@Home project has emerged as a key weapon to deal with the new pandemic situation. FoundationOne Liquid Assay (F1L) is a next-generation sequences-based liquid biopsy service, able to detect 324 molecular alterations and genomic signatures, from May 2020 available at patients’ home (FMI-Liquid@Home). We analyzed time and costs saving for patients with cancer, their caregivers and National Healthcare System (NHS) with FMI-Liquid@Home versus F1L performed at our Department. Different variables have been evaluated. Between May 2020 and August 2021, 218 FMI-Liquid@Home were performed for patients with cancer in Italy. Among these, our Department performed 153 FMI-Liquid@Home with the success rate of 98% (vs. 95% for F1L in the hospital). Time saving for patients and their caregivers was 494.86 and 427.36 hours, respectively, and costs saving was 13 548.70€. Moreover, for working people these savings were 1084.71 hours and 31 239.65€, respectively. In addition, the total gain for the hospital was 163.5 hours and 6785€, whereas for NHS was 1084.71 hours and 51 573.60€, respectively. FMI-Liquid@Home service appears to be useful and convenient allowing time and costs saving for patients, caregivers, and NHS. Born during the COVID-19 pandemic, it could be integrated in oncological daily routine in the future. Therefore, additional studies are needed to better understand the overall gain and how to integrate this service in different countries.     

Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.     

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.

Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.

Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.

Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.     

Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan,January 25-26, 2019)

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).Key words: respiratory failure, muscular dystrophy, cough efficacy, spirometry, polygraphy, non-invasive ventilation, arterial blood gases, cough machine, invasive ventilation, tracheostomy, mechanical ventilation