Alessia Bramanti

Permutation Disalignment Index as an Indirect, EEG-Based, Measure of Brain Connectivity in MCI and AD Patients

OBJECTIVE In this work, we introduce Permutation Disalignment Index (PDI) as a novel nonlinear, amplitude independent, robust to noise metric of coupling strength between time series, with the aim of applying it to electroencephalographic (EEG) signals recorded longitudinally from Alzheimers Disease (AD) and Mild Cognitive Impaired (MCI) patients. The goal is to indirectly estimate the connectivity between the cortical areas, through the quantification of the coupling strength between the corresponding EEG signals, in order to find a possible matching with the diseases progression. METHOD PDI is first defined and tested on simulated interacting dynamic systems. PDI is then applied to real EEG recorded from 8 amnestic MCI subjects and 7 AD patients, who were longitudinally evaluated at time [Formula: see text]0 and 3 months later (time [Formula: see text]1). At time [Formula: see text]1, 5 out of 8 MCI patients were still diagnosed MCI (stable MCI) whereas the remaining 3 exhibited a conversion from MCI to AD (prodromal AD). PDI was compared to the Spectral Coherence and the Dissimilarity Index. RESULTS Limited to the size of the analyzed dataset, both Coherence and PDI resulted sensitive to the conversion from MCI to AD, even though only PDI resulted specific. In particular, the intrasubject variability study showed that the three patients who converted to AD exhibited a significantly ([Formula: see text]) increased PDI (reduced coupling strength) in delta and theta bands. As regards Coherence, even though it significantly decreased in the three converted patients, in delta and theta bands, such a behavior was also detectable in one stable MCI patient, in delta band, thus making Coherence not specific. From the Dissimilarity Index point of view, the converted MCI showed no peculiar behavior. CONCLUSIONS PDI significantly increased, in delta and theta bands, specifically in the MCI subjects who converted to AD. The increase of PDI reflects a reduced coupling strength among the brain areas, which is consistent with the expected connectivity reduction associated to AD progression.

Label-free quantification of the effects of lithium niobate polarization on cell adhesion via holographic microscopy

The surface of a c- cut ferroelectric crystal at room temperature is characterized by the so-called screening surface charges, able to compensate the charge due to the spontaneous polarization. Recently, these charges inspired the investigation of the interaction affinity of live cells with lithium niobate and lithium tantalate crystals. However, different knowledge gaps still remain that prevent a reasonable application of these materials for biological applications. Here, a label-free holographic total internal reflection microscopy is shown; the technique is able to evaluate quantitatively the contact area of live fibroblast cells adhering onto the surface of a ferroelectric lithium niobate crystal. The results show values of contact area significantly different between cells adhering onto the positive or negative face of the crystal. This reinforces the reasons for using the polarization charge of these materials to study and/or control cellular processes and, thus, to develop an innovative platform based on polar dielectric functional substrates.

Transcriptomic analysis of gingival mesenchymal stem cells cultured on 3D bioprinted scaffold: A promising strategy for neuroregeneration

The combined approach of mesenchymal stem cells (MSCs) and scaffolds has been proposed as a potential therapeutic tool for the treatment of neurodegenerative diseases. Indeed, even if MSCs can promote neuronal regeneration, replacing lost neurons or secreting neurotrophic factors, many limitations still exist for their application in regenerative medicine, including the low survival and differentiation rate. The scaffolds, by mimicking the endogenous microenvironment, have shown to promote cell survival, proliferation, and differentiation. In this work, gingival mesenchymal stem cells (GMSCs), isolated from healthy donors, were expanded in vitro, by culturing them adherent in plastic dishes (CTR-GMSCs) or on a poly(lactic acid) scaffold (SC-GMSCs). In order to evaluate the survival and the neurogenic differentiation potential, we performed a comparative transcriptomic analysis between CTR-GMSCs and SC-GMSCs by next generation sequencing. We found that SC-GMSCs showed an increased expression of neurogenic and prosurvival genes. In particular, genes involved in neurotrophin signaling and PI3K/Akt pathways were upregulated. On the contrary, proapoptotic and negative regulator of neuronal growth genes were downregulated. Moreover, nestin and GAP-43 protein levels increased in SC-GMSCs, confirming the neurogenic commitment of these cells. In conclusion, the scaffold, providing a trophic support for MSCs, may promote GMSCs differentiation toward a neuronal phenotype and survival.

Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: a new tool for bone defect repair

BackgroundThe role of bone tissue engineering in the field of regenerative medicine has been a main research topic over the past few years. There has been much interest in the use of three-dimensional (3D) engineered scaffolds (PLA) complexed with human gingival mesenchymal stem cells (hGMSCs) as a new therapeutic strategy to improve bone tissue regeneration. These devices can mimic a more favorable endogenous microenvironment for cells in vivo by providing 3D substrates which are able to support cell survival, proliferation and differentiation. The present study evaluated the in vitro and in vivo capability of bone defect regeneration of 3D PLA, hGMSCs, extracellular vesicles (EVs), or polyethyleneimine (PEI)-engineered EVs (PEI-EVs) in the following experimental groups: 3D-PLA, 3D-PLA + hGMSCs, 3D-PLA + EVs, 3D-PLA + EVs + hGMSCs, 3D-PLA + PEI-EVs, 3D-PLA + PEI-EVs + hGMSCs.MethodsThe structural parameters of the scaffold were evaluated using both scanning electron microscopy and nondestructive microcomputed tomography. Nanotopographic surface features were investigated by means of atomic force microscopy. Scaffolds showed a statistically significant mass loss along the 112-day evaluation.ResultsOur in vitro results revealed that both 3D-PLA + EVs + hGMSCs and 3D-PLA + PEI-EVs + hGMSCs showed no cytotoxicity. However, 3D-PLA + PEI-EVs + hGMSCs exhibited greater osteogenic inductivity as revealed by morphological evaluation and transcriptomic analysis performed by next-generation sequencing (NGS). In addition, in vivo results showed that 3D-PLA + PEI-EVs + hGMSCs and 3D-PLA + PEI-EVs scaffolds implanted in rats subjected to cortical calvaria bone tissue damage were able to improve bone healing by showing better osteogenic properties. These results were supported also by computed tomography evaluation that revealed the repair of bone calvaria damage.ConclusionThe re-establishing of the integrity of the bone lesions could be a promising strategy in the treatment of accidental or surgery trauma, especially for cranial bones.

Naturally occurring compounds in differentiation based therapy of cancer

Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.

Pyroelectric Effect Enables Simple and Rapid Evaluation of Biofilm Formation

Biofilms are detrimental to human life and industrial processes due to potential infections, contaminations, and deterioration. Therefore, the evaluation of microbial capability to form biofilms is of fundamental importance for assessing how different environmental factors may affect their vitality. Nowadays, the approaches used for biofilm evaluation are still poor in reliability and rapidity and often provide contradictory results. Here, we present what we call biofilm electrostatic test (BET) as a simple, rapid, and highly reproducible tool for evaluating in vitro the ability of bacteria to form biofilms through electrostatic interaction with a pyroelectrified carrier. The results show how the BET is able to produce viable biofilms with a density 6-fold higher than that on the control, after just 2 h incubation. The BET could pave the way to a rapid standardization of the evaluation of bacterial resistance among biofilm-producing microorganisms. In fact, due to its simplicity and cost-effectiveness, it is well suited for a rapid and easy implementation in a microbiology laboratory.

Advances in assessing myotonia: Can sensor-engineered glove have a role?

Non-dystrophic (NDMs) and Dystrophic Myotonias (DMs) are diseases characterized by the presence of myotonia with or without muscle weakness. A standardized myotonia assessment is important to more objectively quantify the handgrip myotonia. We screened 10 patients affected by NDM and 10 patients with DM, using the sensor-engineered glove (SEG). The time required to perform a complete finger extension (grip myotonia time, GMT) at maximum velocity (MV) after maximum voluntary contraction (MVC) was evaluated through an ad hoc protocol including rest, exercise, and ice effects on handgrip myotonia. We observed a general trend to GMT increase when applying the ice block and a GMT decrease when repeating GM movements, at individual level in both NDM and DM patients. SEG is an automated, non-invasive, quick, and easy technique for evaluating handgrip myotonia in NDM and DM patients. SEG could, therefore, be considered a promising tool to evaluate myotonia and monitor treatment efficacy for clinical trials.

Telemedicine for Facio-Scapulo-Humeral Muscular Dystrophy: A multidisciplinary approach to improve quality of life and reduce hospitalization rate?

BACKGROUND Facio-Scapulo-Humeral Muscular Dystrophy (FSHD) is an autosomal dominant inherited disorder characterized by a variable and asymmetric involvement of facial, trunk, upper and lower extremity muscles. Although respiratory weakness is a relatively unknown feature of FSHD, it is not rare. Telemedicine has been used in a variety of health care fields, but only recently, with the advent of sophisticated technology, its interest among health professionals became evident, even in such diseases. OBJECTIVE To demonstrate the telemedicine efficacy in FSHD. METHODS Four siblings affected by a severe form of FSHD, living in a rural area far away from the referral center for neuromuscular diseases, who used a wheelchair, suffered from chronic respiratory failure and were provided with long-term non-invasive mechanical ventilation, received a 6-month period of telemedicine support. This consisted of video conferencing (respiratory physiotherapy, psychological support, neurological and pneumological assessment, nurse-coach supervision) and telemonitoring of cardiorespiratory variables (oxygen saturation, blood pressure, and heart rate). RESULTS We performed 540 video conference sessions per patient, including three daily contacts with short monitoring oximetry measurements, blood pressure, and heart-rate measurements, psychological support, neurological and pneumological assessment, nurse-coach supervision. CONCLUSIONS Our findings indicate that our telemedicine system was user-friendly, efficient for the home treatment of FSHD, and allowed reducing hospital admissions.

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Purpose The combination of oral derived stem cells and 3-D scaffolds is considered advantageous in bone repair. In particular, collagen membranes possess ideal biological properties and can support infiltration and proliferation of osteoblasts, promoting bone regeneration. Our study aimed to develop a new biocompatible osteogenic construct composed of a commercially available collagen membrane (Evolution [Evo]), human periodontal-ligament stem cells (hPDLSCs) enriched with extracellular vesicles (EVs), or polyethylenimine (PEI)-engineered EVs (PEI-EVs). Methods Osteogenic ability and expression of osteogenic genes were evaluated in vitro in hPDLSCs cultured with or without Evo, with Evo and EVs, or PEI-EVs. In addition, the bone-regeneration capacity of Evo, Evo enriched with hPDLSCs, Evo enriched with hPDLSCs and EVs/PEI-EVs was investigated in rats subjected to calvarial defects. Results Our results showed that Evo enriched with EVs and PEI-EVs showed high biocompatibility and osteogenic properties in vitro and in vivo. In addition, quantitative reverse-transcription polymerase chain reaction demonstrated the upregulation of osteogenic genes, such as TGFB1, MMP8, TUFT1, TFIP11, BMP2, and BMP4, in the presence of PEI-EVs. Upregulation of BMP2/4 was confirmed for Evo enriched with PEI-EVs and hPDLSCs both in vitro by Western blot and in vivo by immunofluorescence. Conclusion Our results indicated that Evo enriched with hPDLSCs and PEI-EVs is able to promote a bone-regeneration process for the treatment of calvarium and ossification defects caused by accidental or surgery trauma. In particular, PEI-EVs had a significant role in activation of the osteogenic process.

Label-Free Optical Marker for Red-Blood-Cell Phenotyping of Inherited Anemias

The gold-standard methods for anemia diagnosis are complete blood counts and peripheral-smear observations. However, these do not allow for a complete differential diagnosis as that requires biochemical assays, which are label-dependent techniques. On the other hand, recent studies focus on label-free quantitative phase imaging (QPI) of blood samples to investigate blood diseases by using video-based morphological methods. However, when sick cells are very similar to healthy ones in terms of morphometric features, identification of a blood disease becomes challenging even with QPI. Here, we introduce a label-free optical marker (LOM) to detect red-blood-cell (RBC) phenotypes, demonstrating that a single set of all-optical parameters can clearly identify a signature directly related to an erythrocyte disease through modeling each RBC as a biological lens. We tested this novel biophotonic analysis by proving that several inherited anemias, such as iron-deficiency anemia, thalassemia, hereditary spherocytosis, and congenital dyserythropoietic anemia, can be identified and sorted, thus opening a novel route for blood diagnosis on a completely different concept based on LOMs.