Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

Exploring ChatGPT's potential in the clinical stream of neurorehabilitation.

In several medical fields, generative AI tools such as ChatGPT have achieved optimal performance in identifying correct diagnoses only by evaluating narrative clinical descriptions of cases. The most active fields of application include oncology and COVID-19-related symptoms, with preliminary relevant results also in psychiatric and neurological domains. This scoping review aims to introduce the arrival of ChatGPT applications in neurorehabilitation practice, where such AI-driven solutions have the potential to revolutionize patient care and assistance. First, a comprehensive overview of ChatGPT, including its design, and potential applications in medicine is provided. Second, the remarkable natural language processing skills and limitations of these models are examined with a focus on their use in neurorehabilitation. In this context, we present two case scenarios to evaluate ChatGPT ability to resolve higher-order clinical reasoning. Overall, we provide support to the first evidence that generative AI can meaningfully integrate as a facilitator into neurorehabilitation practice, aiding physicians in defining increasingly efficacious diagnostic and personalized prognostic plans.

MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment.

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.

Alarmins in cutaneous malignant melanoma: An updated overview of emerging evidence on their pathogenetic, diagnostic, prognostic, and therapeutic role.

Malignant cutaneous melanoma is the leading cause of death for skin cancer to date, with globally increasing incidence rates. In this epidemiological scenario, international scientific research is exerting efforts to identify new clinical strategies aimed at the prognostic amelioration of the disease. Very promising and groundbreaking in this context is the scientific interest related to alarmins and their pioneering utility in the setting of the pathogenetic understanding, diagnosis, prognosis, and therapy for malignant cutaneous melanoma. However, the scientific investigations on this matter should not overlook their still well-presented dual and contradictory role. The aim of our critical analysis is to provide an up-to-date overview of the emerging evidence concerning the dichotomous role of alarmins in the aforementioned clinical settings. Our literature revision was based on the extensive body of both preclinical and clinical findings published on the PubMed database over the past 5 years. In addition to this, we offer a special focus on potentially revolutionary new therapeutic frontiers, which, on the strength of their earliest successes in other clinical areas, could inaugurate a new era of personalized and precision medicine in the field of dermato-oncology.

Beneficial Effect of Olive Oil and Its Derivates: Focus on Hematological Neoplasm.

Olive oil (Olea europaea) is one of the major components of the Mediterranean diet and is composed of a greater percentage of monounsaturated fatty acids, such as oleic acid; polyunsaturated fatty acids, such as linoleic acid; and minor compounds, such as phenolic compounds, and particularly hydroxytyrosol. The latter, in fact, are of greater interest since they have found widespread use in popular medicine. In recent years, it has been documented that phenolic acids and in particular hydroxytyrosol have anti-inflammatory, antioxidant, and antiproliferative action and therefore interest in their possible use in clinical practice and in particular in neoplasms, both solid and hematological, has arisen. This work aims to summarize and analyze the studies present in the literature, both in vitro and in vivo, on the possible use of minor components of olive oil in some hematological neoplasms. In recent years, in fact, interest in nutraceutical science has expanded as a possible adjuvant in the treatment of neoplastic pathologies. Although it is worth underlining that, regarding the object of our study, there are still few preclinical and clinical studies, it is, however, possible to document a role of possible interest in clinical practice.

Oxidative Stress and Chronic Myeloid Leukemia: A Balance between ROS-Mediated Pro- and Anti-Apoptotic Effects of Tyrosine Kinase Inhibitors.

The balanced reciprocal translocation t (9; 22) (q34; q11) and the BCR-ABL fusion gene, which produce p210 bcr-abl protein production with high tyrosine kinase activity, are characteristics of chronic myeloid leukemia, a myeloproliferative neoplasm. This aberrant protein affects several signaling pathways connected to both apoptosis and cell proliferation. It has been demonstrated that tyrosine kinase inhibitor treatment in chronic myeloid leukemia acts by inducing oxidative stress and, depending on its level, can activate signaling pathways responsible for either apoptosis or survival in leukemic cells. Additionally, oxidative stress and reactive oxygen species generation also mediate apoptosis through genomic activation. Furthermore, it was shown that oxidative stress has a role in both BCR-ABL-independent and BCR-ABL-dependent resistance pathways to tyrosine kinases, while patients with chronic myeloid leukemia were found to have a significantly reduced antioxidant level. The ideal environment for tyrosine kinase inhibitor therapy is produced by a favorable oxidative status. We discuss the latest studies that aim to manipulate the redox system to alter the apoptosis of cancerous cells.

Potential New Therapies "ROS-Based" in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis.

Chronic lymphocytic leukemia, in spite of recent advancements, is still an incurable disease; the majority of patients eventually acquire resistance to treatment through relapses. In all subtypes of chronic lymphocytic leukemia, the disruption of normal B-cell homeostasis is thought to be mostly caused by the absence of apoptosis. Consequently, apoptosis induction is crucial to the management of this illness. Damaged biological components can accumulate as a result of the oxidation of intracellular lipids, proteins, and DNA by reactive oxygen species. It is possible that cancer cells are more susceptible to apoptosis because of their increased production of reactive oxygen species. An excess of reactive oxygen species can lead to oxidative stress, which can harm biological elements like DNA and trigger apoptotic pathways that cause planned cell death. In order to upset the balance of oxidative stress in cells, recent therapeutic treatments in chronic lymphocytic leukemia have focused on either producing reactive oxygen species or inhibiting it. Examples include targets created in the field of nanomedicine, natural extracts and nutraceuticals, tailored therapy using biomarkers, and metabolic targets. Current developments in the complex connection between apoptosis, particularly ferroptosis and its involvement in epigenomics and alterations, have created a new paradigm.

Artificial Intelligence: A Snapshot of Its Application in Chronic Inflammatory and Autoimmune Skin Diseases.

Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies.

Metaverse in Mental Health: The Beginning of a Long History.

PURPOSE OF REVIEW: We review the first pilot studies applying metaverse-related technologies in psychiatric patients and discuss the rationale for using this complex federation of technologies to treat mental diseases. Concerning previous virtual-reality applications in medical care, metaverse technologies provide the unique opportunity to define, control, and shape virtual scenarios shared by multi-users to exploit the "synchronized brains" potential exacerbated by social interactions. RECENT FINDINGS: The application of an avatar-based sexual therapy program conducted on a metaverse platform has been demonstrated to be more effective concerning traditional sexual coaching for treating female orgasm disorders. Again, a metaverse-based social skills training program has been tested on children with autism spectrum disorders, demonstrating a significant impact on social interaction abilities. Metaverse-related technologies could enable us to develop new reliable approaches for treating diseases where behavioral symptoms can be addressed using socio-attentive tasks and social-interaction strategies.

Dynamics of astrocytes Ca2+ signaling: a low-cost fluorescence customized system for 2D cultures.

In an effort to help reduce the costs of fluorescence microscopy and expand the use of this valuable technique, we developed a low-cost platform capable of visualising and analysing the spatio-temporal dynamics of intracellular Ca2+ signalling in astrocytes. The created platform, consisting of a specially adapted fluorescence microscope and a data analysis procedure performed with Imagej Fiji software and custom scripts, allowed us to detect relative changes of intracellular Ca2+ ions in astrocytes. To demonstrate the usefulness of the workflow, we applied the methodology to several in vitro astrocyte preparations, specifically immortalised human astrocyte cells and wild-type mouse cells. To demonstrate the reliability of the procedure, analyses were conducted by stimulating astrocyte activity with the agonist dihydroxyphenylglycine (DHPG), alone or in the presence of the antagonist 2-methyl-6-phenylethyl-pyridine (MPEP).

Exploring the Therapeutic Potential of Ganoderma lucidum in Cancer.

Triterpenoids, such as ganoderic acid, and polysaccharides, including ß-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types and has shown an anti-proliferative activity, especially in leukemia, lymphoma, and myeloma lines. Moreover, research clarified the capability of molecules from Ganoderma lucidum to induce mitochondrial damage in acute promyelocytic leukemia cells, without cytotoxic effects in normal mononuclear cells. Active lipids extracted from the spores of this fungus have also been shown to induce apoptosis mediated by downregulation of P-Akt and upregulation of caspases-3, -8, and -9. Among in vivo studies, a study in BALB/c mice injected with WEHI-3 leukemic cells suggested that treatment with Ganoderma lucidum promotes differentiation of T- and B-cell precursors, phagocytosis by PBMCs, and NK cell activity. Our review presents data revealing the possibility of employing Ganoderma lucidum in hematological malignancies and incorporating it into clinical practice.

Multiparametric Evaluation of Geriatric Patients Admitted to Intermediate Care: Impact on Geriatric Rehabilitation.

Optimizing the functional status of patients of any age is a major global public health goal. Rehabilitation is a process in which a person with disabilities is accompanied to achieve the best possible physical, functional, social, intellectual, and relational outcomes. The Intermediate Care Unit within the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa is focused on the treatment and motor reactivation of patients with geriatric pathologies. The objective of this study was to identify which factor, among the characteristics related to the patient and those identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes. Our findings revealed significant correlations between the Barthel Index delta, the 4AT Screening Test, and the number of drugs taken. This association highlights the potential benefits of medication management in enhancing the overall well-being and functional abilities of frail older adults, despite the literature suggesting that polypharmacotherapy is associated with a reduction in functional status and an increase in mortality. These findings underscore the significance of a multidimensional geriatric assessment. Refining and optimising these multidisciplinary approaches is the objective of a more effective geriatric rehabilitation strategy.

Application of Machine Learning Algorithms for Prognostic Assessment in Rotator Cuff Pathologies: A Clinical Data-Based Approach.

AIM: The overall aim of this proposal is to ameliorate the care of rotator cuff (RC) tear patients by applying an innovative machine learning approach for outcome prediction after arthroscopic repair. MATERIALS AND METHODS: We applied state-of-the-art machine learning algorithms to evaluate the best predictors of the outcome, and 100 RC patients were evaluated at baseline (T0), after 1 month (T1), 3 months (T2), 6 months (T3), and 1 year (T4) from surgical intervention. The outcome measure was the Costant-Murley Shoulder Score, whereas age, sex, BMI, the 36-Item Short-Form Survey, the Simple Shoulder Test, the Hospital Anxiety and Depression Scale, the American Shoulder and Elbow Surgeons Score, the Oxford Shoulder Score, and the Shoulder Pain and Disability Index were considered as predictive factors. Support vector machine (SVM), k-nearest neighbors (k-NN), naïve Bayes (NB), and random forest (RF) algorithms were employed. RESULTS: Across all sessions, the classifiers demonstrated suboptimal performance when using both the complete and shrunken sets of features. Specifically, the logistic regression (LR) classifier achieved a mean accuracy of 46.5% ± 6%, while the random forest (RF) classifier achieved 51.25% ± 4%. For the shrunken set of features, LR obtained a mean accuracy of 48.5% ± 6%, and RF achieved 45.5% ± 4.5%. No statistical differences were found when comparing the performance metrics of ML algorithms. CONCLUSIONS: This study underlines the importance of extending the application of AI methods to new predictors, such as neuroimaging and kinematic data, in order to better record significant shifts in RC patients' prognosis. LIMITATIONS: The data quality within the cohort could represent a limitation, since certain variables, such as smoking, diabetes, and work injury, are known to have an impact on the outcome.

Alexithymia and asthma: a systematic review.

Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of alexithymia in patients affected by asthma and clarify its associations with other involved psychological and physical factors. In January 2023, according to PRISMA guidelines, a systematic search using PubMed and Scopus was conducted. Twenty-six studies were eligible based on inclusion criteria. Alexithymia was significantly present in asthma patients, with most studies reporting a higher prevalence (from 9 to 62.8%) than in control groups (approximately 10%). The coexistence of asthma and alexithymia was associated with a worse quality of life, psychiatric comorbidity, poor symptom control, and difficulty in recognizing exacerbations of the disease. These results suggest that alexithymia can negatively impact the management of asthma. For this reason, we recommend an accuracy assessment in clinical settings and the implementation of psychological interventions to promote the emotional and physical wellbeing of asthmatic patients.

Information and communication technologies-based interventions for children with autism spectrum conditions: a systematic review of randomized control trials from a positive technology perspective.

Information and communication technologies (ICTs) have become more widely used in the past years to help people with autism spectrum conditions (ASC). Serious games embedded into computers or tablets, as well as social robots, are the most employed ICT-related tools that are appealing to and appropriate for autistic children. The goal of ICT applications is to enhance behavioral abnormalities associated with ASC while also creating an interactive link between one person and one computer. Comparatively, to human-based therapy, ICT tools aid to inspire autistic children by providing predictability and regularity of tasks. Regaining social skills is the primary behavioral goal for which ICT tools have been designed and implemented. In the past several years, many studies have been created to show how effective it is at improving targeted behaviors. However, only a small number of researchers have used an RCT approach to evaluate its effectiveness. In this systematic review, we only included RCT studies where ICT technologies were used to help children with ASC in improving their social skills. Only 14 RCT studies satisfied the criteria and 12 described significant improvements, showing how the use of technology in educational contexts produced better improvement in developing several social skill facets with respect to the traditional face-to-face approach. Some studies used interventions and outcome measures focused on the core ASC symptoms, but many others addressed neurocognitive functions directly, like social cognition or emotional regulation, while other more general functions such as language or adaptive behaviors. We propose a classification based on processes and outcome measures to foster future research in this specific area of research. The behavioral intervention mediated by technological tools such as computer-based, tablet, and social robotics, undoubtedly provides a comfortable environment that promotes constant learning for people with ASC. Evidence provided in this review highlights the translational potential of this field of study in primary care practice and educational settings.

"Mens Sana in Cute Sana"-A State of the Art of Mutual Etiopathogenetic Influence and Relevant Pathophysiological Pathways between Skin and Mental Disorders: An Integrated Approach to Contemporary Psychopathological Scenarios.

The negative socioeconomic impact of mental health disorders and skin diseases has increased in part due to the conflict between Russia and Ukraine, which has been a fertile ground for the emergence of psychopathologies. It is firmly established that there is a direct thread of etiopathogenetic communication between skin diseases and neuropsychiatric disorders, and the literature has tried to reveal the pathophysiological mechanisms governing such bidirectionality. This paper discusses this complex network of molecular pathways that are targeted by conventional and biological pharmacological agents that appear to impact two pathological spheres that previously seemed to have little connection. This molecular discussion is supplemented with a literature review, from a clinical viewpoint, regarding skin-brain etiopathogenetic bidirectionality. We focus on post-traumatic stress disorder (PTSD), which can be considered for all intents and purposes a systemic inflammatory disease that also affects the skin. A brief overview is also provided on the diagnostic-therapeutic and follow-up potential of oxidative and inflammatory markers potentially involved in the pathophysiological mechanisms treated. The aim is to clarify how these mechanisms may be useful in defining different stress-coping strategies and thus individual phenotypes of stress sensitivity/resistance in order to promote personalized medicine in the field of psychodermatology.

Role of Gut Microbiota in Overweight Susceptibility in an Adult Population in Italy.

Although the gut microbiota is known to affect body weight, its relationship with overweight/obesity is unclear. Our aim was to characterize microbiota composition in a cohort from the southernmost area of Italy. We investigated whether an altered gut microbiota could play an etiological role in the pathogenesis of overweight/obesity. A total of 163 healthy adults were enrolled. Microbiome analysis was performed via 16S rRNA gene sequencing. We found significant phylum variations between overweight (N = 88) and normal-weight (N = 75) subjects. Bacteroidetes and Proteobacteria were higher in overweight participants (p = 0.004; p = 0.03), and Firmicutes and Verrucomicrobia were lower (p = 0.02; p = 0.008) compared to normal-weight participants. Additionally, Akkermansia and Bifidobacterium (genus level) were significantly lower in the overweight group, as well as Akkermansia muciniphila at the species level. The Firmicutes/Bacteroidetes ratio (F/B ratio), an index of dysbiosis, was found to be inversely associated with BMI in linear and logistic regression models (p = 0.001; p = 0.005). The association remained statistically significant after adjustment for potential confounders. This cross-sectional study contributes to defining the gut microbiota composition in an adult population living in southern Italy. It confirms the relationship between overweight susceptibility and the dysbiosis status, highlighting the possible etiological role of the F/B ratio in disease susceptibility.

Gender Differences in Oxidative Stress in Relation to Cancer Susceptibility and Survival.

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

Talking about Sexuality in Stroke Individuals: The New Era of Sexual Rehabilitation.

One of the largest causes of mortality and disability worldwide is stroke. In the last twenty years significant objectives have been achieved in the early and chronic treatment of motor and cognitive dysfunctions, increasing the quality of life in patients and their caregivers. However, there is an unresolved clinical issue that remains: sexual dysfunctions. Multiple etiologies, including organic (such as lesion localization, premorbid medical problems, and drugs) and psychosocial (such as fear of recurrences, loss of self-esteem, role shifts, anxiety, and depression), are associated with sexual deficits. In this perspective review, we reported the last piece of evidence about this crucial topic which drastically affects the quality of life of these patients. Indeed, although patients may often not disclose their sexual concerns, literature demonstrates that they seek help concerning this issue. On the other side, clinicians working in the rehabilitation field are not always comfortable or prepared to deal with sexuality and sexual function in neurological patients. A new phase of the training course should be launched including different physicians, nurses, rehabilitation specialists, and social workers, to learn how to deal with topics related to sexuality. As a result, professional sexual counselors should now become a structured part of stroke settings and rehabilitation with new effective tools (i.e., PLISSIT model; TDF program) for improving quality of life.