Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma.

Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25-30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we previously demonstrated that tomato bushy stunt virus (TBSV), functionalized on the surface with CooP peptide, specifically targets MB cells. Here, we tested the hypothesis that TBSV-CooP can specifically deliver a conventional chemotherapeutic drug (i.e., doxorubicin, DOX) to MB in vivo. To this aim, a preclinical study was designed to verify, by histological and molecular methods, if multiple doses of DOX-TBSV-CooP were able to inhibit tumor progression of MB pre-neoplastic lesions, and if a single dose was able to modulate pro-apoptotic/anti-proliferative molecular signaling in full-blown MBs. Our results demonstrate that when DOX is encapsulated in TBSV-CooP, its effects on cell proliferation and cell death are similar to those obtained with a five-fold higher dose of non-encapsulated DOX, both in early and late MB stages. In conclusion, these results confirm that CooP-functionalized TBSV NPs are efficient carriers for the targeted delivery of therapeutics to brain tumors.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment.

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum.

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.

Is psychosocial rehabilitation useful in older people living in nursing homes? A pilot study on long-term cognitive and behavioural outcomes.

BACKGROUND: Age-related changes in cognitive and behavioural functions, although common, may vary considerably across individuals and cognitive domains. There is limited evidence focusing on the benefits of training based on cognitive/social learning principles in the elderly. The aim of this study is to investigate the effects of Assertive Social Skill Training (ASST) in improving cognitive and mood outcomes in a sample of older patients living in a Sicilian nursing home. METHODS: Forty-seven older subjects were enrolled in this case-control study. Each participant was evaluated by a neuropsychologist, through the administration of a short psychometric battery using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Geriatric Depression Scale (GDS), at three time points: before (T0), immediately following (T1), and 6 months after the end of the training (T2). Both groups received cognitive behavioural therapy and psychological support, but the experimental group received the ASST protocol (60 sessions, five times a week, for 12 weeks, each session lasting about 60 min), whilst the control group participated in group meetings with recreational activities. RESULTS: Post-hoc analysis showed that only patients receiving ASST presented a statistically significant improvement in global cognitive functions (MMSE: P < 0.001), frontal abilities (FAB: P < 0.001), and mood (GDS: P < 0.001); these positive outcomes were maintained at T2. CONCLUSIONS: Promising treatments, like the ASST, aimed at potentiating cognitive, behavioural, and social skills, are needed to improve older people's quality of life, especially when they live in nursing homes.

Assessment and rehabilitation of cognitive deficit in a Niemann-Pick type C disease patient.

Niemann-Pick type C (NP-C) disease is a lipid storage disorder characterized by visceral (hepatosplenomegaly) and neurological symptoms: ataxia, dystonia, cognitive disorder, psychiatric disorder, and vertical supranuclear gaze palsy. Cognitive impairment is one of the core symptoms of NP-C disease, but there are few data about the cognitive rehabilitation treatment in NP-C patients. This case report aims to evaluate the effects of the cognitive rehabilitation treatment of a young woman affected by NP-C. Cognitive rehabilitation was performed with pc-based and paper and pencil exercises. We used a clinical approach that includes psychotherapy-based diagnostic and rehabilitation procedures and neuropsychological methods, using strategies to improve cognitive residual abilities. Our data showed an improvement of cognitive functions and quality of life after an intensive rehabilitation program.

Neuropsychological assessment in Niemann-Pick disease type C: a systematic review.

BACKGROUND: The neuropsychological profile of Niemann-Pick type C (NP-C) patients is characterized by an early deterioration in executive functions and attention. There are few studies on cognitive impairment and on neuropsychological assessment of NP-C disease. The purpose of this review is to analyze the studies on a psychological assessment for NP-C patients. METHOD: This review aims to identify a neuropsychological assessment to evaluate cognitive domains and neuropsychological changes in these patients. There were a total of 73 articles. The search terms were identified as titles and abstracts. All articles were evaluated by title, abstract, and text. RESULTS: Only four of the 73 articles were included because they met the criteria of our review. Furthermore, in these studies, possible diagnostic protocols are proposed on NP-C subjects. DISCUSSION AND CONCLUSION: The cognitive impairment in NP-C has a negative impact on daily functioning and quality of life. Early diagnosis could identify cognitive deficits and promote cognitive interventions to improve the neuropsychological profile. The management of NP-C disease should be based on a multidisciplinary approach, to treating symptoms, preserving neurological functions, and guaranteeing the best possible quality of life. Early identification of neurological and psychological symptoms of the disease is necessary in order to decrease the progression of neurological disease and improve patient care and treatment outcomes. Furthermore, research should focus more on cognitive aspects, not only in the diagnostic process but also in the rehabilitation process.

How patients with mild dementia living in a nursing home benefit from dementia cafés: a case-control study focusing on psychological and behavioural symptoms and caregiver burden.

BACKGROUND: Dementia is a syndrome, mainly due to neurodegeneration, affecting cognition, behaviour, feelings and relationships. Pharmacological treatment is still challenging and thus different ways to improve/slow down the disease are necessary. METHODS: Twenty-five subjects with mild dementia, living in a nursing home, and their relatives were invited to attend a dementia cafe, a community group which provides support for families affected by dementia. Each patient was evaluated by a neuropsychologist, through the administration of a specific neuropsychological battery, before and at the end of the study. Their outcomes were compared to a matched group of patients with dementia receiving psycho-counselling. RESULTS: After the dementia cafe meetings, patients showed higher significant changes in mood (P < 0.01), behavioural symptoms (P < 0.001), quality of life (P < 0.001), and caregiver burden (P < 0.001). The control group significantly improved only in quality of life with a reduction of caregiver burden. CONCLUSIONS: Our findings confirm that patients with dementia may benefit from the dementia cafe, especially concerning behavioural symptoms. Moreover, caregivers find these cafés to be welcoming, relaxed places to socialise and access support and information. Future dementia cafés should create programs and comfortable environments answering to the different needs of the patients.

Do patients with PD benefit from music assisted therapy plus treadmill-based gait training? An exploratory study focused on behavioral outcomes.

Purpose: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, presenting not only with motor symptoms (resting tremor, bradykinesia, and muscular rigidity), but also with cognitive and behavioral problems that need to be addressed in a rehabilitation setting. Aim of the study was to evaluate the effects of a combined rehabilitative approach, using gait training coupled to music-based therapy, on cognitive and behavioral function in a sample of patients with PD.Materials and Methods: Forty patients, meeting the inclusion criteria, were enrolled in this study and were randomly divided into two groups. The control group (CG) underwent traditional over ground gait training, whilst the experimental group (EG) underwent gait training with the Biodex Gait Trainer 3 (a treadmill integrated with music therapy). Each subject was evaluated at baseline (T0) and after the training (T1), using specific neuropsychological and motor function tests.Results: The EG presented higher outcomes scores concerning mood and quality of life in all subscales of Psychological General Well-Being Index (i.e. anxiety, depression, health, vitality and positivity) and subscales of Brief-COPE, with regard to behavioral disengagement, positive reframing, planning, acceptance and use of emotional support, as compared to the CG. Moreover, a significant improvement in motor functioning, with regard to static and dynamic balance, was found in the EG.Conclusion: Music-based gait training rehabilitation may be considered an effective strategy to improve behavioral performances, coping strategies and rehabilitation outcomes in patients with PD.

The role of music therapy in rehabilitation: improving aphasia and beyond.

Music is part of the human nature, and it is also philogenically relevant to language evolution. Language and music are bound together in the enhancement of important social functions, such as communication, cooperation and social cohesion. In the last few years, there has been growing evidence that music and music therapy may improve communication skills (but not only) in different neurological disorders. One of the plausible reasons concerning the rational use of sound and music in neurorehabilitation is the possibility to stimulate brain areas involved in emotional processing and motor control, such as the fronto-parietal network. In this narrative review, we are going to describe the role of music therapy in improving aphasia and other neurological disorders, underlying the reasons why this tool could be effective in rehabilitative settings, especially in individuals affected by stroke.

Effects of virtual reality-based training with BTs-Nirvana on functional recovery in stroke patients: preliminary considerations.

AIM OF THE STUDY: Cognitive impairment occurs frequently in post-stroke patients. This study aimed to determine the effects of a virtual reality training (VRT) with BTs-Nirvana (BTsN) on the recovery of cognitive functions in stroke patients, using the Interactive-Semi-Immersive Program (I-SIP). MATERIALS AND METHODS: We enrolled 12 subjects (randomly divided into two groups: experimental group (EG); and control group (CG)), who attended the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of Messina from January to June 2016. The EG underwent a VRT with BTsN, whereas CG received a standard cognitive treatment. Both the groups underwent the same conventional physiotherapy program. Each treatment session lasted 45 minutes and was repeated three times a week for 8 weeks. All the patients were evaluated by a specific clinical-psychometric battery before (T0), immediately (T1), and one month (T2) after the end of the training. RESULTS: At T1, the EG presented a greater improvement in the trunk control test (p = 0.03), the Montreal Cognitive Assessment (p = 0.01), the selective attention assessment scores (p = 0.01), the verbal memory (p = 0.03), and the visuospatial and constructive abilities (p = 0.01), as compared to CG. Moreover, such amelioration persisted at T2 only in the EG. CONCLUSIONS: According to these preliminary data, VRT with I-SIP can be considered a useful complementary treatment to potentiate functional recovery, with regard to attention, visual-spatial deficits, and motor function in patients affected by stroke.

Improving Cognitive Function in Patients with Stroke: Can Computerized Training Be the Future?

BACKGROUND: Cognitive impairment after stroke is common and can cause disability with a high impact on quality of life and independence. Cognitive rehabilitation is a therapeutic approach designed to improve cognitive functioning after central nervous system's injuries. Computerized cognitive rehabilitation (CCR) uses multimedia and informatics resources to optimize cognitive compromised performances. The aim of this study is to evaluate the effects of pc cognitive training with Erica software in patients with stroke. METHODS: We studied 35 subjects (randomly divided into 2 groups), affected by either ischemic or hemorrhagic stroke, having attended from January 2013 to May 2015 the Laboratory of Robotic and Cognitive Rehabilitation of Istituto di Ricerca e Cura a Carattere Scientifico Neurolesi in Messina. Cognitive dysfunctions were investigated through a complete neuropsychological battery, administered before (T0) and after (T1) each different training. RESULTS: At T0, all the patients showed language and cognitive deficits, especially in attention process and memory abilities, with mood alterations. After the rehabilitation program (T1), we noted a global cognitive improvement in both groups, but a more significant increase in the scores of the different clinical scales we administered was found after CCR. CONCLUSIONS: Our data suggest that cognitive pc training by using the Erica software may be a useful methodology to increase the post-stroke cognitive recovery.

Computerized Training in Poststroke Aphasia: What About the Long-Term Effects? A Randomized Clinical Trial.

BACKGROUND: Poststroke aphasia is a very disabling disorder, which may affect speech expression, comprehension, and reading or writing. Treatment of aphasia should be initiated as soon as possible after the brain injury; however, the improvement of language functions can occur also in the chronic phase. MATERIALS AND METHODS: Thirty-two patients were randomly assigned to either an experimental group (17 patients) treated with computerized rehabilitation training (Power-Afa, Maddaloni, Campania, Italy) or a control group (15 patients), submitted to conventional speech therapy. Patients were trained 3 times a week for 8 weeks, (i.e., 24 sessions of 45 minutes each), and assessed at baseline (T0), at the end of each training (T1), and 3 months after the end of the treatment (T2). RESULTS: The experimental group had a significant improvement from T0 to T1 in all the outcomes, whereas for the control group patients such an improvement was significant only concerning Functional Independence Measure and ideomotor praxis. Notably, the improvements in cognitive and language functions were maintained at 3-month follow-up only in the experimental group. CONCLUSIONS: The software Power-Afa can be considered a valuable tool in improving the linguistic and cognitive recovery in patients affected by poststroke aphasia in the chronic phase. Further studies with larger samples and longer follow-up periods are needed to confirm such promising findings.

The Patched 1 tumor-suppressor gene protects the mouse lens from spontaneous and radiation-induced cataract.

Age-related cataract is the most common cause of visual impairment. Moreover, traumatic cataracts form after injury to the eye, including radiation damage. We report herein that sonic hedgehog (Shh) signaling plays a key role in cataract development and in normal lens response to radiation injury. Mice heterozygous for Patched 1 (Ptch1), the Shh receptor and negative regulator of the pathway, develop spontaneous cataract and are highly susceptible to cataract induction by exposure to ionizing radiation in early postnatal age, when lens epithelial cells undergo rapid expansion in the lens epithelium. Neonatally irradiated and control Ptch1(+/-) mice were compared for markers of progenitors, Shh pathway activation, and epithelial-to-mesenchymal transition (EMT). Molecular analyses showed increased expression of the EMT-related transforming growth factor ß/Smad signaling pathway in the neonatally irradiated lens, and up-regulation of mesenchymal markers Zeb1 and Vim. We further show a link between proliferation and the stemness property of lens epithelial cells, controlled by Shh. Our results suggest that Shh and transforming growth factor ß signaling cooperate to promote Ptch1-associated cataract development by activating EMT, and that the Nanog marker of pluripotent cells may act as the primary transcription factor on which both signaling pathways converge after damage. These findings highlight a novel function of Shh signaling unrelated to cancer and provide a new animal model to investigate the molecular pathogenesis of cataract formation.

Cognitive training for patients with dementia living in a sicilian nursing home: a novel web-based approach.

Dementia is an increasing challenge for health care and social system in developed countries. Interventions with a cognitive focus, also using assistive technology, are leading to promising results in improving cognitive and behavior symptoms in individuals with dementia. Aim of our study was to evaluate the combined effects of the standard cognitive training in addition to web-based rehabilitation in dementia people living in a nursing home. We have studied twenty dementia people (10 females and 10 males) with a mild to moderate cognitive decline (MMSE 25 ± 3.4) associated to moderate behavioral alterations, and mainly due to vascular causes. These patients were randomly assigned to one of two groups (experimental or standard treatment-namely the control group). All participants in the experimental group completed the specific training, consisting of 24 sessions of web-based cognitive training, for 8 weeks, in addition to standard rehabilitation. Each participant was evaluated by a skilled neuropsychologist before and after each treatment. The experimental group had a statistically significant change of the Geriatric Depression Scale (p = 0.03), Constructive Apraxia (p < 0.001), Matrices Attentive (p = 0.01), and Mini Mental State Examination (p = 0.04). Web-based cognitive rehabilitation can be useful in improving cognitive performance, besides psychological well-being, in demented individuals living in home care.

Developmental and oncogenic radiation effects on neural stem cells and their differentiating progeny in mouse cerebellum.

Neural stem cells are highly susceptible to radiogenic DNA damage, however, little is known about their mechanisms of DNA damage response (DDR) and the long-term consequences of genotoxic exposure. Patched1 heterozygous mice (Ptc1(+/-)) provide a powerful model of medulloblastoma (MB), a frequent pediatric tumor of the cerebellum. Irradiation of newborn Ptc1(+/-) mice dramatically increases the frequency and shortens the latency of MB. In this model, we investigated the mechanisms through which multipotent neural progenitors (NSCs) and fate-restricted progenitor cells (PCs) of the cerebellum respond to DNA damage induced by radiation, and the long-term developmental and oncogenic consequences. These responses were assessed in mice exposed to low (0.25 Gy) or high (3 Gy) radiation doses at embryonic day 13.5 (E13.5), when NSCs giving rise to the cerebellum are specified but the external granule layer (EGL) has not yet formed, or at E16.5, during the expansion of granule PCs to form the EGL. We found crucial differences in DDR and apoptosis between NSCs and fate-restricted PCs, including lack of p21 expression in NSCs. NSCs also appear to be resistant to oncogenesis from low-dose radiation exposure but more vulnerable at higher doses. In addition, the pathway to DNA repair and the pattern of oncogenic alterations were strongly dependent on age at exposure, highlighting a differentiation-stage specificity of DNA repair pathways in NSCs and PCs. These findings shed light on the mechanisms used by NSCs and PCs to maintain genome integrity during neurogenesis and may have important implications for radiation risk assessment and for development of targeted therapies against brain tumors.

Parental involvement in robot-mediated intervention: a systematic review.

Introduction: Over the years, the conceptual approach to pediatric rehabilitation has reevaluated the parent's role in the therapeutic process, considering parental involvement as a necessary condition for the effectiveness of the intervention. In the field of pediatric intervention, the therapeutic use of robots represents a growing clinical interest, but the feasibility and applicability of these robotic interventions, including those involving parents, remain unclear. This systematic review aims to investigate parental involvement in robot-mediated interventions (RMI) for children and adolescents in the current literature. Our main goal is to analyze and summarize all existing studies to discuss and draw future research directions and implications for clinical practice. Method: After collecting results from 1,106 studies, the studies selected were analyzed using thematic analysis. The literature review was conducted in accordance with the PRISMA guidelines by searching databases such as PubMed and Web of Science until 07 February 2023. Studies that met the following inclusion criteria were included: (1) the use of a robot as a therapeutic-rehabilitation tool and (2) the presence/involvement of parents/caregivers in child-robot therapeutic sessions. Results: A total of 10 articles were included. The extracted data included study design, participant characteristics, type of robot used, outcome measures, aim, and type of intervention. The results reveal that parental involvement in RMI could be feasible and useful in improving intervention efficacy, particularly in improving the child's social-communicative abilities and the caregiver's educational skills. Discussion: RMI intervention with parental participation could be a useful therapeutic strategy in pediatrics. However, to date, few studies have investigated this specific topic, and the reported results may enhance future research to understand its effectiveness in specific areas of use. Systematic review registration: identifier: CRD42024553214.

Improvement of Self-Esteem in Children with Specific Learning Disorders after Donkey-Assisted Therapy.

Dyslexia is a learning disorder related to receptive language characterized by difficulties with decoding, fluent word recognition, automatic naming skills and/or reading comprehension skills. It usually leads to severe functional impairment and the permanent need for support and interventions. Since animal-assisted interventions (AAIs) have been found to improve physical, emotional, cognitive and/or social functioning in humans, the aim of this study is to demonstrate the effectiveness of onotherapy on children with SLD by improving self-esteem and school performance. Sixteen patients with a diagnosis of dyslexia were randomly assigned to two treatment groups: the first was a conventional neuropsychological group therapy without onotherapy, and the second was a neuropsychological group therapy incorporating AAIs with therapy donkeys. The neuropsychological assessment included the WISC-IV, DDE and the TMA test, which were administered before and after the treatment in both groups. The results of the experimental group show significant improvement in word reading test correctness (p = 0.03) and speed (p = 0.03), non-word reading test speed (p = 0.01), reading text test correctness (p = 0.05) and speed (p = 0.03), word writing test correctness (p = 0.01), non-word writing test correctness (p = 0.02), writing sentences with homophonic words correctness (p = 0.01), interpersonal TMA (p = 0.04) and the total TMA (p = 0.04), which were significative. On the other hand, in the control group, significant differences were found in word reading test speed (p = 0.01), non-word reading test speed (p = 0.04), reading text test speed (p = 0.02), writing word test correctness (p = 0.01), writing non-word test correctness (p = 0.01) and writing sentences with homophonic words (p = 0.01). However, in this group, we observed no significant difference in the esteem of children. Training associated with the donkeys determined improved scholastic performances as far as reading is concerned and a change in self-esteem. Therefore, we can state that AAIs for dyslexia could be a viable and effective option to enhance the rehabilitation process, increase self-esteem and improve cognitive functions and language skills recovery.

Multisensory stimulation and rehabilitation for disability improvement: Lessons from a case report.

RATIONALE: Spastic quadriplegia is most severe form of Infantile Cerebral Palsy. Patients are unable to use their legs, arms and body and show language disorder and profound intellectual disability. The treatment of patients diagnosed with spastic quadriplegia is complex and multidisciplinary. In this case report we described the positive effect of multisensory environment (MSEs) rehabilitation, and the strategies and technologies used to provide child who have to severe spastic quadriplegia and intellectual disability, palsy with playful and fun activities designed according to his abilities. PATIENT CONCERN: A 7-years-old boy diagnosed with spastic quadriplegia and severe intellectual disability began rehabilitation by MSEs. DIAGNOSES: Spastic quadriplegia is most severe form of Infantile Cerebral Palsy. Patients are unable to use their legs, arms and body and show language disorder and profound intellectual disability. INTERVENTIONS: Multisensory room is a large environment containing various elements where child can interact spontaneously and independently. OUTCOMES: The comparison scores between T0-T1 showed a reduction in self-harm and motor stereotypies (hand flapping). Sustained attention was improved and we observed a better therapeutic compliance by means of greater involvement in gaming activities. CONCLUSION: The stimuli within the MSEs provided the child opportunities to express himself with facilities more suited to his potential. Future research should project designed randomized controlled trials to examine the efficacy of multisensory on reduction disability.

Use of Virtual Reality in Children with Dyslexia.

In recent years, the study of dyslexia has seen rapid progress in definition and classification, neuropsychological correlates, neurobiological factors, and intervention. However, there are few studies on how virtual reality can affect improving cognitive domains and cross-cutting pedagogical skills. We, therefore, tested intervention through the use of a virtual reality rehabilitation system (VRRS) in children with dyslexia. Twenty-eight patients diagnosed with dyslexia were enrolled in this study. One-half underwent conventional neuropsychological treatment, and the other half performed VR neurorehabilitation training using the VRRS. All patients were evaluated by neuropsychological assessment at baseline (T0) and at the end of the protocol (T1). The assessment included the administration of the Wechsler Intelligence Scale for Children-IV and the Italian Battery for the Assessment of Dyslexia and Dysorthography. Our results showed a significant difference in word-reading test scores as well as in homophonic writing. In addition, treatment type was found to affect some domains of the WISC. We believe that the VRRS led to improved outcomes through the use of VR, which encourages active exploration, improves engagement, and provides motivation and enjoyment, allowing longer training sessions and improving treatment adherence.

MiRNA-Mediated Fibrosis in the Out-of-Target Heart following Partial-Body Irradiation.

Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the pathogenesis of RIHD was investigated. C57Bl/6J female mice were whole- (WBI) or partial-body-irradiated (PBI) with 2 Gy of X-rays or sham-irradiated (SI). In PBI exposure, the lower third of the mouse body was irradiated, while the upper two-thirds were shielded. From all groups, hearts were collected 15 days or 6 months post-irradiation. The MiRNome analysis at 15 days post-irradiation showed that miRNAs, belonging to the myomiR family, were highly differentially expressed in WBI and PBI mouse hearts compared with SI hearts. Raman spectral data collected 15 days and 6 months post-irradiation showed biochemical differences among SI, WBI and PBI mouse hearts. Fibrosis in WBI and PBI mouse hearts, indicated by the increased deposition of collagen and the overexpression of genes involved in myofibroblast activation, was found 6 months post-irradiation. Using an in vitro co-culture system, involving directly irradiated skeletal muscle and unirradiated ventricular cardiac human cells, we propose the role of miR-1/133a as mediators of the abscopal response, suggesting that miRNA-based strategies could be relevant for limiting tissue-dependent reactions in non-directly irradiated tissues.