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1.
Sensors (Basel) ; 23(6)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36991904

ABSTRACT

Axial postural abnormalities (aPA) are common features of Parkinson's disease (PD) and manifest in over 20% of patients during the course of the disease. aPA form a spectrum of functional trunk misalignment, ranging from a typical Parkinsonian stooped posture to progressively greater degrees of spine deviation. Current research has not yet led to a sufficient understanding of pathophysiology and management of aPA in PD, partially due to lack of agreement on validated, user-friendly, automatic tools for measuring and analysing the differences in the degree of aPA, according to patients' therapeutic conditions and tasks. In this context, human pose estimation (HPE) software based on deep learning could be a valid support as it automatically extrapolates spatial coordinates of the human skeleton keypoints from images or videos. Nevertheless, standard HPE platforms have two limitations that prevent their adoption in such a clinical practice. First, standard HPE keypoints are inconsistent with the keypoints needed to assess aPA (degrees and fulcrum). Second, aPA assessment either requires advanced RGB-D sensors or, when based on the processing of RGB images, they are most likely sensitive to the adopted camera and to the scene (e.g., sensor-subject distance, lighting, background-subject clothing contrast). This article presents a software that augments the human skeleton extrapolated by state-of-the-art HPE software from RGB pictures with exact bone points for posture evaluation through computer vision post-processing primitives. This article shows the software robustness and accuracy on the processing of 76 RGB images with different resolutions and sensor-subject distances from 55 PD patients with different degrees of anterior and lateral trunk flexion.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/diagnosis , Posture/physiology , Software , Videotape Recording , Bone and Bones , Postural Balance/physiology
2.
Int J Mol Sci ; 24(7)2023 Mar 28.
Article in English | MEDLINE | ID: mdl-37047310

ABSTRACT

(1) Inverse psoriasis (IP), also known as intertriginous, typically affects the groin, armpits, navel, intergluteal fissure, and external genitalia. Skin lesions are erythematous plaques of inflammatory nature, smooth, well-delimited, non-scaly, and non-infiltrated. Lesions may be accompanied by itching, pain, or burning sensation. The aim of this study is both to investigate the modulation of the skin microbiota induced by IP and, on the other hand, to test the effectiveness of the new biotechnological product LimpiAL 2.5%. (2) Patients affected by IP were recruited in a private practice and treated for 4 weeks with LimpiAL 2.5% exclusively. The clinical effects on the lesion skin were evaluated, and the skin microbiotas before and after treatment were compared. (3) The clinical outcomes reveled a significant beneficial effect of the tested product. At the same time, LimpiAL increased the biological diversity of the skin microbiota and exerted a significant decrease of some Corynebacterium species, and the increase of some Staphylococcus species. (4) Together, the clinical outcomes and the microbiota analysis suggest that LimpiAL treatment improves the skin condition of affected patients, basically restoring the eubiosis conditions of the affected sites and modulating the bacterial composition of the resident microbiota.


Subject(s)
Microbiota , Psoriasis , Humans , Psoriasis/drug therapy , Skin/pathology , Erythema/pathology , Pruritus/pathology
3.
Int J Mol Sci ; 24(21)2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37958915

ABSTRACT

The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Liposomes , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Phospholipids , Virosomes , Drug Resistance, Bacterial , Bacteria
4.
Curr Issues Mol Biol ; 44(5): 2321-2334, 2022 May 19.
Article in English | MEDLINE | ID: mdl-35678687

ABSTRACT

In recent years, alongside the conventional screening procedures for the evaluation of probiotics for human usage, the pharmaceutical and food industries have encouraged scientific research towards the selection of new probiotic bacterial strains with particular functional features. Therefore, this study intended to explore novel functional properties of five Lactiplantibacillus plantarum strains isolated from bee bread. Specifically, antioxidant, antimicrobial and ß-glucosidase activities, exopolysaccharides (EPS) production and the ability to synthesize γ-aminobutyric acid (GABA) were evaluated. The results demonstrated that the investigated L. plantarum strains were effective in inhibiting the growth of some human opportunistic pathogens in vitro (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Enterococcus faecalis and Staphylococcus aureus). Moreover, the evaluation of antioxidant and ß-glucosidase activity and of EPS and GABA production, revealed a different behavior among the strains, testifying how these properties are strongly strain-dependent. This suggests that a careful selection within a given species is important in order to identify appropriate strains for specific biotechnological applications. The results highlighted that the five strains of L. plantarum are promising candidates for application as dietary supplements in the human diet and as microbial cultures in specific food productions.

5.
Sensors (Basel) ; 22(6)2022 Mar 10.
Article in English | MEDLINE | ID: mdl-35336311

ABSTRACT

Dravet syndrome (DS) is a rare and severe form of genetic epilepsy characterized by cognitive and behavioural impairments and progressive gait deterioration. The characterization of gait parameters in DS needs efficient, non-invasive quantification. The aim of the present study is to apply nonlinear indexes calculated from inertial measurements to describe the dynamics of DS gait. Twenty participants (7 M, age 9-33 years) diagnosed with DS were enrolled. Three wearable inertial measurement units (OPAL, Apdm, Portland, OR, USA; Miniwave, Cometa s.r.l., Italy) were attached to the lower back and ankles and 3D acceleration and angular velocity were acquired while participants walked back and forth along a straight path. Segmental kinematics were acquired by means of stereophotogrammetry (SMART, BTS). Community functioning data were collected using the functional independence measure (FIM). Mean velocity and step width were calculated from stereophotogrammetric data; fundamental frequency, harmonic ratio, recurrence quantification analysis, and multiscale entropy (τ = 1...6) indexes along anteroposterior (AP), mediolateral (ML), and vertical (V) axes were calculated from trunk acceleration. Results were compared to a reference age-matched control group (112 subjects, 6-25 years old). All nonlinear indexes show a disruption of the cyclic pattern of the centre of mass in the sagittal plane, quantitatively supporting the clinical observation of ataxic gait. Indexes in the ML direction were less altered, suggesting the efficacy of the compensatory strategy (widening the base of support). Nonlinear indexes correlated significantly with functional scores (i.e., FIM and speed), confirming their effectiveness in capturing clinically meaningful biomarkers of gait.


Subject(s)
Epilepsies, Myoclonic , Wearable Electronic Devices , Adolescent , Adult , Biomechanical Phenomena , Child , Gait , Humans , Walking , Young Adult
6.
BMC Neurol ; 21(1): 332, 2021 Aug 30.
Article in English | MEDLINE | ID: mdl-34461838

ABSTRACT

BACKGROUND: The consequences of strict COVID-19 mobility restrictions on motor/non-motor features in Parkinson's disease (PD) have not been systematically studied but worse mobility and quality of life have been reported. To elucidate this question, 12 mild to moderate PD patients were assessed in March 2020 before and after two months of isolation as part of a clinical study that had to be interrupted due to the pandemic and the implementation of COVID19 mobility restrictions. METHODS: Twelve patients were systematically evaluated before and after the lockdown period as part of a larger cohort that previously underwent thermal water rehabilitation. Clinical outcomes were the Body Mass index, the Mini-Balance Evaluation Systems Test, the MDS-Unified Parkinson's Disease Rating Scale part III, the 6 Minute Walking Test and the New Freezing of Gait Questionnaire. Global cognition was evaluated with the Montreal Cognitive Assessment scale. The impact of COVID-19 restrictions on quality of life and functional independence was evaluated with The Parkinson's disease Quality of life (PDQ-39), the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living questionnaires (IADL) and the Parkinson's disease cognitive functional rating scales (PD-CFRS). RESULTS: After two months of isolation the Mini-BESTest score worsened (p=0.005), and four patients reported one or more falls during the lockdown. BMI increased (p=0.031) while the remaining clinical variables including quality of life did not change. CONCLUSION: We observed moderate worsening at Mini-BESTest, greater risk of falls and increased body weight as consequence of prolonged immobility. We believe negative effects were partially softened since patients were in contact with our multidisciplinary team during the lockdown and had previously received training to respond to the needs of this emergency isolation. These findings highligh the importnace of patient-centered interventions in PD management.


Subject(s)
COVID-19 , Gait Disorders, Neurologic , Mobility Limitation , Parkinson Disease , Accidental Falls , Activities of Daily Living , Communicable Disease Control , Gait Disorders, Neurologic/etiology , Humans , Male , Parkinson Disease/complications , Quality of Life , Risk , SARS-CoV-2
7.
New Microbiol ; 44(1): 42-50, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33453704

ABSTRACT

This work aims to assess the in vitro adhesion of two type strains of Lactobacillus plantarum (ATCC 14917 and ATCC BAA-793) (now Lactiplantibacillus plantarum). The experiments were conducted both in vitro on colon cells lines (Caco-2 and HT-29) and in vivo by adopting Galleria mellonella, a well-known alternative preclinical model. Data comparison obtained from in vitro and in vivo assays showed that adhesion performance is comparable in both models. Moreover, the type strain BAA-793, originally isolated from human saliva, showed enhanced adhesion performance, either in vitro to the low mucus-producing cell line (HT-29) or in vivo into the G mellonella gut. These results suggest a possible adaptation of this strain to its ecological niche compared to ATCC 14917. This preliminary pilot study, once again, showed the reliability of G. mellonella oral administration model as a first-line screening tool for in vitro to in vivo translation. Also, for the first time, the permanence of Lactobacillus strains into G. mellonella gut has been reported, reinforcing the claim that this preclinical model can be used, together with standardised in vitro and in vivo procedures already accepted across the scientific community, for the evaluation and investigation of new potential probiotic strains.


Subject(s)
Lactobacillus plantarum , Lepidoptera , Probiotics , Administration, Oral , Animals , Bacterial Adhesion , Caco-2 Cells , Humans , Pilot Projects , Reproducibility of Results
8.
Entropy (Basel) ; 23(5)2021 May 11.
Article in English | MEDLINE | ID: mdl-34064732

ABSTRACT

Stroke is the commonest cause of disability. Novel treatments require an improved understanding of the underlying mechanisms of recovery. Fractal approaches have demonstrated that a single metric can describe the complexity of seemingly random fluctuations of physiological signals. We hypothesize that fractal algorithms applied to electroencephalographic (EEG) signals may track brain impairment after stroke. Sixteen stroke survivors were studied in the hyperacute (<48 h) and in the acute phase (∼1 week after stroke), and 35 stroke survivors during the early subacute phase (from 8 days to 32 days and after ∼2 months after stroke): We compared resting-state EEG fractal changes using fractal measures (i.e., Higuchi Index, Tortuosity) with 11 healthy controls. Both Higuchi index and Tortuosity values were significantly lower after a stroke throughout the acute and early subacute stage compared to healthy subjects, reflecting a brain activity which is significantly less complex. These indices may be promising metrics to track behavioral changes in the very early stage after stroke. Our findings might contribute to the neurorehabilitation quest in identifying reliable biomarkers for a better tailoring of rehabilitation pathways.

9.
Acta Haematol ; 143(2): 155-162, 2020.
Article in English | MEDLINE | ID: mdl-31533096

ABSTRACT

Refractory anaemia (RA) among myelodysplastic syndrome (MDS) is associated with a partial functional iron deficit and may require transfusions. In low-risk lymphoma and solid tumour patients, iron support improves erythropoietin (EPO) cost-effectiveness in treating anaemia. The aim of this study is to see if oral sucrosomial iron support improves the cost-effectiveness of EPO treatment in MDS patients affected by low-risk RA. We treated patients with EPO only or with EPO plus oral sucrosomial iron or intravenous (i.v.) iron. The need for transfusions was lowest in the group taking oral iron (p = 0.016) or not receiving supplementation at all (p = 0.022). We compared costs of EPO with i.v. ferric gluconate or oral sucrosomial iron supplementation or no iron supplementation. The oral iron group had fewer side effects, fewer patient medical visits in the out-patient setting, and fewer transfusions; this led to higher savings on direct hospital costs and indirect patient costs (lost days at work) and translated into a 50% abatement of overall expenditures. EPO treatment-related expenditures in MDS-RA patients were lowest with oral sucrosomial iron supplementation (Sideral®), with a longer interval between EPO administration in maintenance treatment, quicker hemoglobin recovery, lower ferritin increase and fewer blood transfusions.


Subject(s)
Anemia, Refractory/drug therapy , Erythropoietin/therapeutic use , Iron/administration & dosage , Myelodysplastic Syndromes/pathology , Aged , Aged, 80 and over , Anemia, Refractory/complications , Anemia, Refractory/economics , Dietary Supplements , Disease Progression , Erythropoietin/economics , Female , Ferric Compounds/administration & dosage , Ferritins/blood , Health Care Costs , Humans , Italy , Male , Myelodysplastic Syndromes/complications , Treatment Outcome
10.
Sensors (Basel) ; 21(1)2020 Dec 28.
Article in English | MEDLINE | ID: mdl-33379174

ABSTRACT

Freezing of Gait (FoG) is a common symptom in Parkinson's Disease (PD) occurring with significant variability and severity and is associated with increased risk of falls. FoG detection in everyday life is not trivial, particularly in patients manifesting the symptom only in specific conditions. Various wearable devices have been proposed to detect PD symptoms, primarily based on inertial sensors. We here report the results of the validation of a novel system based on a pair of pressure insoles equipped with a 3D accelerometer to detect FoG episodes. Twenty PD patients attended a motor assessment protocol organized into eight multiple video recorded sessions, both in clinical and ecological settings and both in the ON and OFF state. We compared the FoG episodes detected using the processed data gathered from the insoles with those tagged by a clinician on video recordings. The algorithm correctly detected 90% of the episodes. The false positive rate was 6% and the false negative rate 4%. The algorithm reliably detects freezing of gait in clinical settings while performing ecological tasks. This result is promising for freezing of gait detection in everyday life via wearable instrumented insoles that can be integrated into a more complex system for comprehensive motor symptom monitoring in PD.


Subject(s)
Gait Disorders, Neurologic , Parkinson Disease , Wearable Electronic Devices , Foot , Gait , Gait Disorders, Neurologic/diagnosis , Humans , Parkinson Disease/diagnosis
11.
Molecules ; 25(21)2020 Oct 29.
Article in English | MEDLINE | ID: mdl-33137930

ABSTRACT

Berberine is an alkaloid of the protoberberine type used in traditional oriental medicine. Its biological activities include documented antibacterial properties against a wide variety of microorganisms; nonetheless, its use against Escherichia coli strains isolated from urinary infections has not yet been widely investigated in vivo. The emergence of antimicrobial resistance requires new therapeutic approaches to ensure the continued effectiveness of antibiotics for the treatment and prevention of urinary infections. Moreover, uropathogenic Escherichia coli (UPEC) has developed several virulence factors and resistance to routine antibiotic therapy. To this end, several in vitro and in vivo tests were conducted to assess the activity of berberine on uropathogenic E. coli strains. Galleria mellonella as an infection model was employed to confirm the in vivo translatability of in vitro data on berberine activity and its influence on adhesion and invasion proprieties of E. coli on human bladder cells. In vitro pre-treatment with berberine was able to decrease the adhesive and invasive UPEC ability. In vivo treatment increased the larvae survival infected with UPEC strains and reduced the number of circulating pathogens in larvae hemolymph. These preliminary findings demonstrated the efficacy and reliability of G. mellonella as in vivo model for pre-clinical studies of natural substances.


Subject(s)
Anti-Bacterial Agents/pharmacology , Berberine/pharmacology , Escherichia coli Infections , Moths/microbiology , Uropathogenic Escherichia coli/growth & development , Animals , Disease Models, Animal , Escherichia coli Infections/drug therapy , Escherichia coli Infections/metabolism , Hemolymph/microbiology , Larva
13.
Medicina (Kaunas) ; 55(10)2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31581595

ABSTRACT

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.


Subject(s)
Hyaluronan Receptors/metabolism , Intramolecular Oxidoreductases/metabolism , Macrophage Migration-Inhibitory Factors/metabolism , Multiple Sclerosis/metabolism , Up-Regulation , Adolescent , Adult , Biomarkers/metabolism , CD4-Positive T-Lymphocytes/metabolism , Female , Humans , Male , Multiple Sclerosis/blood , Young Adult
14.
Int J Mol Sci ; 19(9)2018 Sep 17.
Article in English | MEDLINE | ID: mdl-30227596

ABSTRACT

BACKGROUND: Juvenile dermatomyositis (JDM) is a systemic, autoimmune, interferon (IFN)-mediated inflammatory muscle disorder that affects children younger than 18 years of age. JDM primarily affects the skin and the skeletal muscles. Interestingly, the role of viral infections has been hypothesized. Mammalian 2'-5'-oligoadenylate synthetase (OAS) genes have been thoroughly characterized as components of the IFN-induced antiviral system, and they are connected to several innate immune-activated diseases. The main purpose of the paper is to define the potential interrelationship between the OAS gene family network and the molecular events that characterize JDM along with double-stranded RNA (dsRNA) molecular pathways. METHODS: We analyzed three microarray datasets obtained from the NCBI in order to verify the expression levels of the OAS gene family network in muscle biopsies (MBx) of JDM patients compared to healthy controls. Furthermore, From GSE51392, we decided to select significant gene expression profiles of primary nasal and bronchial epithelial cells isolated from healthy subjects and treated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA), a molecular pattern associated with viral infection. RESULTS: The analysis showed that all OAS genes were modulated in JDM muscle biopsies. Furthermore, 99% of OASs gene family networks were significantly upregulated. Of importance, 39.9% of modulated genes in JDM overlapped with those of primary epithelial cells treated with poly(I:C). Moreover, the microarray analysis showed that the double-stranded dsRNA virus gene network was highly expressed. In addition, we showed that the innate/adaptive immunity markers were significantly expressed in JDM muscles biopsies. and that their levels were positively correlated to OAS gene family expression. CONCLUSION: OAS gene expression is extremely modulated in JDM as well as in the dsRNA viral gene network. These data lead us to speculate on the potential involvement of a viral infection as a trigger moment for this systemic autoimmune disease. Further in vitro and translational studies are needed to verify this hypothesis in order to strategically plan treatment interventions.


Subject(s)
2',5'-Oligoadenylate Synthetase/genetics , Dermatomyositis/genetics , Gene Regulatory Networks , Multigene Family , Transcriptome , 2',5'-Oligoadenylate Synthetase/immunology , Adaptive Immunity , Adolescent , Dermatomyositis/immunology , Female , Gene Expression Regulation , Humans , Immunity, Innate , Male , Poly I-C/immunology , RNA Virus Infections/immunology , RNA, Double-Stranded/immunology , RNA, Viral/immunology
15.
Clin Immunol ; 157(2): 198-204, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25701800

ABSTRACT

Uveitis is a sight-threatening inflammatory disease of the eye which represents the third leading cause of blindness in the developed countries. The conventional pharmacological treatment includes corticosteroids and immunosuppressive agents, which are limited by their side effects. New therapeutic strategies are thus strongly needed. Exogenously-administered carbon monoxide (CO) may represent an effective treatment for conditions characterized by a dysregulated inflammatory response. Carbon monoxide-releasing molecules (CORMs) are a novel group of compounds capable of carrying and liberating controlled quantities of CO. Among CORMs, CORM-A1 represents the first example of water soluble CO releaser. We show here that CORM-A1 under a late prophylactic regime is able to significantly ameliorate the natural course of experimental autoimmune uveoretinitis, a rodent model of immunoinflammatory posterior uveitis. The present study strongly supports the development of CORM-A1 as a potential new drug for treatment of patients with non-infectious posterior uveitis.


Subject(s)
Autoimmune Diseases/immunology , Boranes/pharmacology , Carbonates/pharmacology , RNA, Messenger/drug effects , Retina/drug effects , Retinitis/immunology , T-Lymphocytes, Regulatory/drug effects , Uvea/drug effects , Uveitis/immunology , Animals , Autoimmune Diseases/chemically induced , Autoimmune Diseases/pathology , Cytokines/drug effects , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Female , Gene Expression/drug effects , Peptide Fragments/toxicity , RNA, Messenger/metabolism , Rats , Rats, Inbred Lew , Retina/immunology , Retina/pathology , Retinitis/chemically induced , Retinitis/pathology , Retinol-Binding Proteins/toxicity , Spleen/drug effects , Spleen/metabolism , T-Lymphocytes, Regulatory/immunology , Uvea/immunology , Uvea/pathology , Uveitis/chemically induced , Uveitis/pathology
16.
J Cell Physiol ; 229(12): 1918-25, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24700487

ABSTRACT

Increasing evidence supports the role of epigenetics in the development of autoimmune disorders and the possibility of using epigenetic modifying drugs in the context of MS has not yet been investigated. We have explored the effect of the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) in two murine models of experimental allergic encephalomyelitis (EAE). DAC treatment was associated with a significant amelioration of the clinical and histological hallmarks of EAE in both models. These effects were observed both in prophylactic and therapeutic regimens. The milder course of the disease was associated with a reduction in the number of spinal cord infiltrating lymphocytes and amelioration of the histopathological signs associated with EAE. In addition, increased transcript levels of anti-inflammatory cytokines and decreased mRNA expression of pro-inflammatory mediators were also observed. Finally, DAC treatment increased the percentage of circulating regulatory T cells by inducing Foxp3 expression via demethylation of a CpG island in Foxp3.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Azacitidine/analogs & derivatives , Encephalomyelitis, Autoimmune, Experimental/genetics , Multiple Sclerosis/genetics , Animals , Anti-Inflammatory Agents/administration & dosage , Azacitidine/administration & dosage , Cytokines/metabolism , Decitabine , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Mice , Multiple Sclerosis/pathology , T-Lymphocytes, Regulatory
17.
Comput Biol Med ; 171: 108101, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38340440

ABSTRACT

BACKGROUND AND OBJECTIVE: Motion analysis is crucial for effective and timely rehabilitative interventions on people with motor disorders. Conventional marker-based (MB) gait analysis is highly time-consuming and calls for expensive equipment, dedicated facilities and personnel. Markerless (ML) systems may pave the way to less demanding gait monitoring, also in unsupervised environments (i.e., in telemedicine). However,scepticism on clinical usability of relevant outcome measures has hampered its use. ML is normally used to analyse treadmill walking, which is significantly different from the more physiological overground walking. This study aims to provide end-users with instructions on using a single-camera markerless system to obtain reliable motion data from overground walking, while clinicians will be instructed on the reliability of obtained quantities. METHODS: The study compares kinematics obtained from ML systems to those concurrently obtained from marker-based systems, considering different stride counts and subject positioning within the capture volume. RESULTS: The findings suggest that five straight walking trials are sufficient for collecting reliable kinematics with ML systems. Precision on joint kinematics decreased at the boundary of the capture volume. Excellent correlation was found between ML and MB systems for hip and knee angles (0.92

Subject(s)
Gait Analysis , Gait , Humans , Reproducibility of Results , Gait/physiology , Walking/physiology , Knee Joint/physiology , Biomechanical Phenomena
18.
Article in English | MEDLINE | ID: mdl-39310783

ABSTRACT

Purpose: The most prevalent treatment-related side effect related to adjuvant radiotherapy (RT) for breast cancer is acute skin toxicity in the irradiated area. The purpose of this single-institution pilot study is to provide preliminary clinical results on the feasibility and safety of a breast ultra-hypofractionated radiation treatment delivered using an automated hybrid-VMAT technique. Skin damage was assessed both with clinical examination and objectively using a Cutometer equipment. Patients and Methods: Patients received 26 Gy to the whole breast and 30 Gy to the tumoral bed in 5 fractions using an automated hybrid-VMAT approach with the option for the breath hold technique if necessary. Acute and late toxicities were clinically evaluated at baseline, 1- and 6-months after treatment using the CTC-AE v.5.0 scale. An instrumental evaluation of the skin elasticity was performed using a Cutometer® Dual MP580. Two parameters per patient, R0 (the total skin firmness) and Q1 (the elastic recovery), were registered at the different timelines. Results: From June 2022 to January 2024, 30 patients, stage T1-T2, N0 were enrolled in the study. Four out of 30 (13.3%) patients reported G2 acute skin toxicities. At 6 months, G2 late toxicity was registered in 3 patients (10%). A total of 2160 measures of R0 and Q1 were recorded. At 1 month after treatment, no correlation was found between measured values of R0 and Q1 and clinical evaluation. At 6 months after treatment, clinical late toxicity ≥1 was strongly associated with decreased R0 and Q1 values ≥24% (p = 0.003) and ≥18% (p = 0.022), respectively. Conclusion: Ultra-hypofractionated whole-breast radiotherapy, when supported by advanced treatment techniques, is both feasible and safe. No severe adverse effects were observed at any of the different timeframes. Acute and late skin toxicities were shown to be lower in contrast to data presented in the literature.

19.
Front Microbiol ; 15: 1441781, 2024.
Article in English | MEDLINE | ID: mdl-39176271

ABSTRACT

Tuberculosis (TB) is a global threat, affecting one-quarter of the world's population. The World Health Organization (WHO) reports that 6 million people die annually due to chronic illnesses, a statistic that includes TB-related deaths. This high mortality is attributed to factors such as the emergence of drug-resistant strains and the exceptional survival mechanisms of Mycobacterium tuberculosis (MTB). Recently, microRNAs (miRNAs) have garnered attention for their crucial role in TB pathogenesis, surpassing typical small RNAs (sRNA) in their ability to alter the host's immune response. For instance, miR-155, miR-125b, and miR-29a have been identified as key players in the immune response to MTB, particularly in modulating macrophages, T cells, and cytokine production. While sRNAs are restricted to within cells, exo-miRNAs are secreted from MTB-infected macrophages. These exo-miRNAs modify the function of surrounding cells to favor the bacterium, perpetuating the infection cycle. Another significant aspect is that the expression of these miRNAs affects specific genes and pathways involved in immune functions, suggesting their potential use in diagnosing TB and as therapeutic targets. This review compiles existing information on the immunomodulatory function of exosomal miRNAs from MTB, particularly focusing on disease progression and the scientific potential of this approach compared to existing diagnostic techniques. Thus, the aim of the study is to understand the role of exosomal miRNAs in TB and to explore their potential for developing novel diagnostic and therapeutic methods.

20.
Front Cell Infect Microbiol ; 14: 1428525, 2024.
Article in English | MEDLINE | ID: mdl-39310784

ABSTRACT

Introduction: Managing burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic. Methods: The antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model. Results and discussion: In vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa. In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model.


Subject(s)
Burns , Disease Models, Animal , Lactobacillales , Larva , Milk, Human , Pseudomonas aeruginosa , Animals , Burns/microbiology , Pseudomonas aeruginosa/drug effects , Humans , Larva/microbiology , Milk, Human/microbiology , Female , Pseudomonas Infections/microbiology , Pseudomonas Infections/drug therapy , Pseudomonas Infections/immunology , Moths/microbiology , Wound Infection/microbiology , Wound Infection/drug therapy , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests
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