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COVID-19 has impacted negatively on the mental health of children with autism spectrum disorder (ASD), as well as on their parents. Remote health services are a sustainable approach to behavior management interventions and to giving caregivers emotional support in several clinical domains. During the COVID-19 pandemic, we investigated the feasibility of a web-based behavioral skills training (BST) program for 16 parents and their children with ASD at home. The BST parent training package was tailored to each different specific behavioral disorder that characterizes children with ASD. After training, we found a significant reduction in the frequency of all the targeted behavioral disorders, as well as an improvement in psychological distress and the perception of the severity of ASD-related symptoms in parents. Our data confirm the efficacy of remote health care systems in the management of behavioral disorders of children with ASD, as well as of their parents during the COVID-19 pandemic.

The consequences of the pandemic on mental health are among the most important side effects of COVID-19. Wide concerns have emerged both regarding vaccine hesitation in the general population, and the vaccine's implementation plan. The aim of this study is to evaluate how the scientific community has investigated the relationship between the COVID-19 vaccine and mental disorders. Contrary to expectations, having a full-blown psychiatric pathology seems to positively affect the attitude towards the vaccine, except for PTSD. The intense fear that accompanied the current world emergency has made this pandemic unique; we discuss how it might be one of the factors involved in this result. Further experimental investigations are needed to estimate how personality traits, hyperarousal, and negative emotions influence vaccine compliance both in the general population and in people living with mental disorders.

This review is a comprehensive analysis of the effects of SARS-CoV-2 infection on Unconventional T cells and innate lymphoid cells (ILCs). COVID-19 affected patients show dysregulation of their adaptive immune systems, but many questions remain unsolved on the behavior of Unconventional cells and ILCs during infection, considering their role in maintaining homeostasis in tissue. Therefore, we highlight the differences that exist among the studies in cohorts of patients who in general were categorized considering symptoms and hospitalization. Moreover, we make a critical analysis of the presence of particular clusters of cells that express activation and exhausted markers for each group in order to bring out potential diagnostic factors unconsidered before now. We also focus our attention on studies that take into consideration recovered patients. Indeed, it could be useful to determine Unconventional T cells' and ILCs' frequencies and functions in longitudinal studies because it could represent a way to monitor the immune status of SARS-CoV-2-infected subjects. Possible changes in cell frequencies or activation profiles could be potentially useful as prognostic biomarkers and for future therapy. Currently, there are no efficacious therapies for SARS-CoV-2 infection, but deep studies on involvement of Unconventional T cells and ILCs in the pathogenesis of COVID-19 could be promising for targeted therapies.

Artificial intelligence has recently modified the panorama of oncology investigation thanks to the use of machine learning algorithms and deep learning strategies. Machine learning is a branch of artificial intelligence that involves algorithms that analyse information, learn from that information, and then employ their discoveries to make abreast choice, while deep learning is a field of machine learning basically represented by algorithms inspired by the organization and function of the brain, named artificial neural networks. In this review, we examine the possibility of the artificial intelligence applications in multiple myeloma evaluation, and we report the most significant experimentations with respect to the machine and deep learning procedures in the relevant field. Multiple myeloma is one of the most common haematological malignancies in the world, and among them, it is one of the most difficult ones to cure due to the high occurrence of relapse and chemoresistance. Machine learning- and deep learning-based studies are expected to be among the future strategies to challenge this negative-prognosis tumour via the detection of new markers for their prompt discovery and therapy selection and by a better evaluation of its relapse and survival.

Recently, a continuous growth for both neurodevelopmental and atopic diseases' incidence was seen throughout the world. Notably, autism spectrum disorders (ASD) and atopic dermatitis (AD) attracted the attention of clinicians and scientists for their impact on the quality of life of patients, starting during childhood. Despite a number of hypotheses about common pathogenesis between the two disorders, uncertainty is still present, and data coming from various parts of the world are contradictory. Fortunately, works recently published have brought useful material for comparative analysis to the benefit of the scientific community, making large scale, country-based perspectives methodologically viable. In light of that, the present study took into account uniform data, available from country-based registries or related publications, dealing with the prevalence of the two conditions around the world, and tried to setup a simple correlation analysis between the two. According to such data, the growth of AD and ASD prevalence appear uncorrelated, leading to hypothesise that, if a common etiopathological pathway exists between the two conditions, they are likely to interact to each other due to a complex interplay of co-morbidities, genes and environmental players not enough explained by a simple correlation analysis. Such facts are worth investigation in future research., (© 2021. The Author(s).)

COVID-19 has caused a public and international health emergency, leading to isolation and social distancing. These restrictions have had a significant impact on the caregivers of people with dementia, increasing the burden of patient management. The purpose of this study was to investigate the stress perceived by caregivers of patients with Alzheimer's disease (AD) during the pandemic. We used a cross-sectional survey design to evaluate the caregivers' psychological responses and coping strategies. Eighty-four caregivers of patients with a diagnosis of AD were involved in this study by completing an online questionnaire. They presented a high perception of stress (the Perceived Stress Scale mean ± DS: 33.5 ± 4.5), and their high burden in caring was mainly related to physical difficulties (Caregiver Burden Inventory-Physical Burden mean ± DS: 15.0 ± 2.1) and perception of loss of time (Caregiver Burden Inventory-Time-dependence Burden mean ± DS: 16.5 ± 1.4). Moreover, caregivers perceived their quality of life as very low (Short Form-12 Health Survey Physical mean ± DS: 13.5 ± 2.7; Short Form-12 Health Survey Mental Health mean ± DS: 16.4 ± 4.2). Finally, we found that participants mostly used dysfunctional coping strategies, such as avoidance strategies (Coping Orientation to Problem Experiences-Avoidance Strategies mean ± DS: 39.5 ± 7.1), but these strategies did not affect the stress level of caregivers. Given that caregivers present a high burden and stress, innovative tools could be a valuable solution to investigate and support their emotional and behavioral status during difficult periods, such as the COVID-19 pandemic.

Atopic dermatitis and psoriasis are two of the most common chronic skin conditions. Current target therapies represent viable and safe solutions for the most severe cases of these two dermatoses but, presently, several limitations exist in terms of efficacy and side effects. A new class of products, epithelium-derived cytokines (TSLP, IL-25, IL-33), show an increasing potential for use in target therapy for these patients, and demonstrate a direct link between a generalized inflammatory and oxidative stress status and the human skin. A review was conducted to better understand their role in the aforementioned conditions. Of these three molecules, TSLP led has been most often considered in studies regarding target therapies, and most of the results in the literature are related to this cytokine. These three cytokines share common stimuli and are linked to each other in both acute and chronic phases of these diseases, and have been challenged as target therapies or biomarkers of disease activity. The results lead to the conclusion that epithelium-derived cytokines could represent a therapeutic opportunity for these patients, especially in itch control. Furthermore, they might work better when paired together with currently available therapies or in combination with in-development treatments. Further studies are needed in order to verify the efficacy and safety of the biologic treatments currently under development.

Background: The COVID-19 pandemic implicated many social restrictions, including the use of distance learning (DL). Indeed, parents were obligated to support their children in online lessons and schoolwork. The aim of this study was to investigate the psycho-emotional impact of the COVID-19 pandemic on parents and children submitted to DL., Methods: One hundred and ninety-two participants (96 parents and 96 children) were enrolled in this study. Parents and children completed an online questionnaire, structured in four sections., Results: The results showed that parents had higher levels of stress and anxiety. In particular, the stress for DL was positively correlated with depression and anxiety. Parents' jobs were negatively correlated with their levels of anxiety and stress. On the other hand, children reported higher levels of depressive symptoms and event-related anxiety, which increased as children got older. The stress and the anxiety in parents were positively correlated with the mood depression and anxiety of their children., Conclusions: The COVID-19 pandemic had a negative impact on the psychological well-being of children and parents who used DL. Although DL could be an alternative teaching method during pandemics, face-to-face teaching is fundamental and irreplaceable as it encourages dialogue, involvement, and human contact.

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aiello, Vagni, Cerasa, Leonardi, Carrozza, Famà, Campisi, Marino, Siracusano, Alquino, Mainiero, Germano, Tartarisco, Pioggia, Gagliano and Ruta.)

Secondary immunodeficiency is reported in most patients with hematological malignancies such as chronic lymphocytic leukemia and multiple myeloma. The aim of our review was to evaluate the existing literature data on patients with hematological malignancies, with regard to the effect of immunodeficiency on the outcome, the clinical and therapeutic approach, and on the onset of noninfectious complications, including thrombosis, pleural effusion, and orofacial complications. Immunodeficiency in these patients has an intense impact on their risk of infection, in turn increasing morbidity and mortality even years after treatment completion. However, these patients with increased risk of severe infectious diseases could be treated with adequate vaccination coverage, but the vaccines' administration can be associated with a decreased immune response and an augmented risk of adverse reactions. Probably, immunogenicity of the inactivated is analogous to that of healthy subjects at the moment of vaccination, but it undertakes a gradual weakening over time. However, the dispensation of live attenuated viral vaccines is controversial because of the risk of the activation of vaccine viruses. A particular immunization schedule should be employed according to the clinical and immunological condition of each of these patients to guarantee a constant immune response without any risks to the patients' health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Allegra, Tonacci, Musolino, Pioggia and Gangemi.)

We provide a conceptual model on the complex interaction between stress, psychological predisposition, and personality traits, accounting for gender, in parents of children with and without autism. We performed a path analysis using a structural equation modeling approach in a sample of parents including 60 ASD and 53 TD couples. In parents of typically developing children (TD), depression level and age are the main direct predictors of stress through the mediating effect of anxiety. Otherwise, in the ASD parent group, the personality trait 'openness' directly predicts the defensive response and stress levels without the mediating effect of anxiety. Our data suggest a route of action in promoting new behavioral strategies to prevent parenting stress, making families run smoothly.

Amyloid precursor protein and its derivates represent a central factor in the process of neurodegeneration in Alzheimer's disease (AD). Since mental illnesses share with AD cognitive impairment, amyloid indicators have been used to explore the unknown pathophysiologic mechanisms underlining psychiatric illness. This work aims to compare the role of amyloid markers, together with tau proteins, among various mental disorders evaluating the possible role of altered amyloid metabolism in the onset and in the course of psychiatric diseases, considering the relationship with cognitive impairment in dementia. This review includes articles written in English, published between 1 January 2011 and 31 January 2021, which evaluated amyloid and tau proteins in psychiatric patients. After screening, 31 studies were included in the review. Results suggest that amyloid metabolism is altered in major psychiatric disorders and that it could be a marker of cognitive impairment. Nevertheless, the role of amyloid in mental diseases seems to be related to neurodevelopmental alteration as well as neurodegeneration processes, like in AD. The role of amyloid in the pathogenesis of mental disorders is still unknown. Amyloid should not be only considered as a marker of cognitive impairment in mental illness, but also for altered neurodevelopment.

COVID-19 has represented an unprecedented challenge to be faced also concerning the spread of information, with scientific literature being often the sole source of trustworthy knowledge for the global community. However, a massive waste in research was noticed during pandemic, preventing the scientists to produce totally novel and original results, and the citizenship to have the complete support they needed from science. The present work investigated the relationship between planned funding, research grants, scientific publications and epidemiology in the 27 EU countries, retrieving a significant correlation between scientific publications and COVID-19 cases and deaths, as well as with economic data. Interestingly, planned coronavirus-devoted funds were correlated with lower GDP per capita and higher mortality, leading to the hypothesis for a lack of translation into real funds allowed to the respective country, or for a significant research waste, not transformed into a tangible product or effect. Such results could suggest the need for a different approach in the future concerning the redistribution of research funds in case of COVID-19 relapse or future pandemic events., (© 2021. The Author(s).)

The current knowledge about the mechanisms of action of light-based treatments (chiefly photodynamic therapy and phototherapy) in skin diseases leans to the possible involvement of epigenetic and oxidative stress mechanisms. To better understand and exploit, to the fullest, these relatively safe and reproducible treatments, several studies have focused on miRNAs, small non-encoding RNAs (22-24 nucleotides), after light-based treatments. The current narrative review focused on 25 articles. A meta-analysis was not deemed appropriate. The results gather the most recurrent skin-related miRNAs up- or downregulated after light treatment. Five of these, miR-21, -29, -125, -145 and -155, are either the most consistently related to efficacy/resistance to treatment or identified as helpful diagnostic tools. A specific class of miRNAs (angioMIRs) requires further studies. Future treatments and imaging techniques could benefit greatly from the use of antagomirs as a possible co-adjuvant therapy along with light-based treatments.

Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a VD receptor, including the brain, heart, stomach, pancreas, skin, gonads, and immune cells, and a deficiency may modify the function of these organs. Thus, the wide-ranging actions of VD help to explain why a reduction in VD amount has been correlated with numerous chronic diseases. In fact, VD deficiency increases the risk of osteoporosis and several other diseases and complications characterized by impaired bone metabolisms, such as autoimmune diseases, inflammatory bowel diseases, allergy, endocrinological diseases, hematological malignancies, and bone marrow transplantation. This review aims to investigate the link between VD deficiency, osteoporosis, and its concomitant diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases; however, adequate vitamin supplementation and restoration of metabolic normality could be useful for better management of these pathologies.

Oxidative stress plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest. In particular, regarding psoriasis, vitiligo, and lichen planus, excess reactive oxygen species and a decline in endogenous antioxidant systems are observed. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. To date, clinical trials in dermatology on these treatments are limited. We reviewed the available studies on the efficacy of antioxidant therapies in psoriasis, vitiligo, and lichen planus. The role of herbal derivatives, vitamins, and trace elements was analyzed. The antioxidant properties of conventional therapies were also evaluated. Data from the literature suggest that antioxidants might be useful, but available studies on this topic are limited, heterogeneous, not completely standardized, and on small populations. Furthermore, in most cases, antioxidants alone are unable to induce significant clinical changes, except perhaps in mild forms, and must be used in conjunction with standard drug treatments to achieve measurable results. Further studies need to be conducted, considering larger populations and using internationally validated scales, in order to compare the results and clinical efficacy.

A plethora of neuroimaging studies have focused on the discovery of potential neuroendophenotypes useful to understand the etiopathogenesis of autism and predict treatment response. Social robotics has recently been proposed as an effective tool to strengthen the current treatments in children with autism. However, the high clinical heterogeneity characterizing this disorder might interfere with behavioral effects. Neuroimaging is set to overcome these limitations by capturing the level of heterogeneity. Here, we provide a preliminary evaluation of the neural basis of social robotics and how extracting neural hallmarks useful to design more effective behavioral applications. Despite the endophenotype-oriented neuroimaging research approach is in its relative infancy, this preliminary evidence encourages innovation to address its current limitations.

Background: Acceptance and Commitment Therapy (ACT) has been demonstrated as effective in improving psychological well-being in several clinical domains, but there is no evidence regarding the parents of children with Autism Spectrum Disorder (ASD)., Methods: In this randomized controlled trial, we evaluated the efficacy of the ACT matrix behavioral protocol in comparison to the Parent Training (PT) program, measuring several primary and secondary outcomes prior to and following treatments. Twelve parents were randomly and equally assigned to two demographically matched groups wherein individuals underwent 24 weekly meetings of ACT protocol (experimental group) or conventional PT (control group)., Results: Parents enrolled in the ACT protocol demonstrated significant improvement in psychological flexibility, awareness states, personal values in everyday life, and parental stress, whereas reduced scores were elicited in parents' perceptions of their child's disruptive behaviors., Conclusions: The results of this randomized controlled trial, if repeated with a large number of subjects, could open the way to include ACT protocols in daily practice to support the development of new parenting skills.

Background: Recently, there has been an increased interest in the efficacy of mindfulness-based interventions (MBI) for people with cardiovascular diseases (CVD), although the exact beneficial effects remain unclear., Methods: This review aims to establish the role of MBI in the management of wellbeing for patients with CVD. Seventeen articles have been included in this systematic synthesis of the literature and eleven in the meta-analysis., Results: Considering physical (i.e., heart rate, blood pressure) and psychological outcomes (i.e., depression, anxiety, stress, styles of coping), the vast majority of studies confirmed that MBI has a positive influence on coping with psychological risk factors, also improving physiological fitness. Random-effects meta-analysis models suggested a moderate-to-large effect size in reducing anxiety, depression, stress, and systolic blood pressure., Conclusions: Although a high heterogeneity was observed in the methodological approaches, scientific literature confirmed that MBI can now be translated into a first-line intervention tool for improving physical and psychological wellbeing in CVD patients., Competing Interests: The authors declare no conflict of interest.

Benzene carcinogenic ability has been reported, and chronic exposure to benzene can be one of the risk elements for solid cancers and hematological neoplasms. Benzene is acknowledged as a myelotoxin, and it is able to augment the risk for the onset of acute myeloid leukemia, myelodysplastic syndromes, aplastic anemia, and lymphomas. Possible mechanisms of benzene initiation of hematological tumors have been identified, as a genotoxic effect, an action on oxidative stress and inflammation and the provocation of immunosuppression. However, it is becoming evident that genetic alterations and the other causes are insufficient to fully justify several phenomena that influence the onset of hematologic malignancies. Acquired epigenetic alterations may participate with benzene leukemogenesis, as benzene may affect nuclear receptors, and provoke post-translational alterations at the protein level, thereby touching the function of regulatory proteins, comprising oncoproteins and tumor suppressor proteins. DNA hypomethylation correlates with stimulation of oncogenes, while the hypermethylation of CpG islands in promoter regions of specific tumor suppressor genes inhibits their transcription and stimulates the onset of tumors. The discovery of the systems of epigenetic induction of benzene-caused hematological tumors has allowed the possibility to operate with pharmacological interventions able of stopping or overturning the negative effects of benzene.

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.

The Hippo/YES-associated protein (YAP) signaling pathway is a cell survival and proliferation-control system with its main activity that of regulating cell growth and organ volume. YAP operates as a transcriptional coactivator in regulating the onset, progression, and treatment response in numerous human tumors. Moreover, there is evidence suggesting the involvement of YAP in the control of the hematopoietic system, in physiological conditions rather than in hematological diseases. Nevertheless, several reports have proposed that the effects of YAP in tumor cells are cell-dependent and cell-type-determined, even if YAP usually interrelates with extracellular signaling to stimulate the onset and progression of tumors. In the present review, we report the most recent findings in the literature on the relationship between the YAP system and hematological neoplasms. Moreover, we evaluate the possible therapeutic use of the modulation of the YAP system in the treatment of malignancies. Given the effects of the YAP system in immunosurveillance, tumorigenesis, and chemoresistance, further studies on interactions between the YAP system and hematological malignancies will offer very relevant information for the targeting of these diseases employing YAP modifiers alone or in combination with chemotherapy drugs.

Mental disorders are common in the general population; every year about 25% of the total European population is affected by a mental condition. The prevalence of psychiatric disorders might be underestimated. Emerging evidence highlights the role of immune response as a key factor in MDs. Immunological biomarkers seem to be related to illness progression and to treatment effectiveness; several studies suggest strong associations among IL-6, TNFa, S100b, IL 1b, and PCR with affective or schizophrenic disorders. The purpose of this review is to examine and to understand the possible link between mental disorders and interleukin 33 to clarify the role of this axis in the immune system. We found 13 research papers that evaluated interleukin 33 or interleukin 31 levels in subjects affected by mental disorders. Eight studies investigated cytokines in affective disorders. Three studies measured levels of IL-33 in schizophrenia and two studies focused on patients affected by autism spectrum disorders. Alterations in brain structure and neurodevelopmental outcome are affected by multiple levels of organization. Disorders of the autoimmune response, and of the IL-33/31 axis, may therefore be one of the factors involved in this process. These results support the evidence that alarmins, particularly the IL-33/31 axis, need more consideration among researchers and practitioners.

In the past two decades, several screening instruments were developed to detect toddlers who may be autistic both in clinical and unselected samples. Among others, the Quantitative CHecklist for Autism in Toddlers (Q-CHAT) is a quantitative and normally distributed measure of autistic traits that demonstrates good psychometric properties in different settings and cultures. Recently, machine learning (ML) has been applied to behavioral science to improve the classification performance of autism screening and diagnostic tools, but mainly in children, adolescents, and adults. In this study, we used ML to investigate the accuracy and reliability of the Q-CHAT in discriminating young autistic children from those without. Five different ML algorithms (random forest (RF), naïve Bayes (NB), support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN)) were applied to investigate the complete set of Q-CHAT items. Our results showed that ML achieved an overall accuracy of 90%, and the SVM was the most effective, being able to classify autism with 95% accuracy. Furthermore, using the SVM-recursive feature elimination (RFE) approach, we selected a subset of 14 items ensuring 91% accuracy, while 83% accuracy was obtained from the 3 best discriminating items in common to ours and the previously reported Q-CHAT-10. This evidence confirms the high performance and cross-cultural validity of the Q-CHAT, and supports the application of ML to create shorter and faster versions of the instrument, maintaining high classification accuracy, to be used as a quick, easy, and high-performance tool in primary-care settings.

This study tested the effectiveness of HeartMan-a mobile personal health system offering decisional support for management of congestive heart failure (CHF)-on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p < 0.001), while the need for sexual counselling decreased in the control group (p < 0.05). Although the group differences were not significant, self-care increased (p < 0.05), and sexual problems decreased (p < 0.05) in the intervention group only. No significant intervention effects were observed for HRQoL, self-care confidence, illness perception and exercise capacity. Overall, results of this proof-of-concept trial suggest that the HeartMan personal health system significantly improved mental and sexual health and self-care behaviour in CHF patients. These observations were in contrast to the lack of intervention effects on HRQoL, illness perception and exercise capacity.

Background: Congestive heart failure (CHF) is a disease that requires complex management involving multiple medications, exercise, and lifestyle changes. It mainly affects older patients with depression and anxiety, who commonly find management difficult. Existing mobile apps supporting the self-management of CHF have limited features and are inadequately validated., Objective: The HeartMan project aims to develop a personal health system that would comprehensively address CHF self-management by using sensing devices and artificial intelligence methods. This paper presents the design of the system and reports on the accuracy of its patient-monitoring methods, overall effectiveness, and patient perceptions., Methods: A mobile app was developed as the core of the HeartMan system, and the app was connected to a custom wristband and cloud services. The system features machine learning methods for patient monitoring: continuous blood pressure (BP) estimation, physical activity monitoring, and psychological profile recognition. These methods feed a decision support system that provides recommendations on physical health and psychological support. The system was designed using a human-centered methodology involving the patients throughout development. It was evaluated in a proof-of-concept trial with 56 patients., Results: Fairly high accuracy of the patient-monitoring methods was observed. The mean absolute error of BP estimation was 9.0 mm Hg for systolic BP and 7.0 mm Hg for diastolic BP. The accuracy of psychological profile detection was 88.6%. The F-measure for physical activity recognition was 71%. The proof-of-concept clinical trial in 56 patients showed that the HeartMan system significantly improved self-care behavior (P=.02), whereas depression and anxiety rates were significantly reduced (P<.001), as were perceived sexual problems (P=.01). According to the Unified Theory of Acceptance and Use of Technology questionnaire, a positive attitude toward HeartMan was seen among end users, resulting in increased awareness, self-monitoring, and empowerment., Conclusions: The HeartMan project combined a range of advanced technologies with human-centered design to develop a complex system that was shown to help patients with CHF. More psychological than physical benefits were observed., Trial Registration: ClinicalTrials.gov NCT03497871; https://clinicaltrials.gov/ct2/history/NCT03497871., International Registered Report Identifier (irrid): RR2-10.1186/s12872-018-0921-2., (©Mitja Luštrek, Marko Bohanec, Carlos Cavero Barca, Maria Costanza Ciancarelli, Els Clays, Amos Adeyemo Dawodu, Jan Derboven, Delphine De Smedt, Erik Dovgan, Jure Lampe, Flavia Marino, Miha Mlakar, Giovanni Pioggia, Paolo Emilio Puddu, Juan Mario Rodríguez, Michele Schiariti, Gašper Slapničar, Karin Slegers, Gennaro Tartarisco, Jakob Valič, Aljoša Vodopija. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 05.03.2021.)

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called "phytochemicals". Most of these substances are responsible for the positive properties of fruits and vegetables, which are an essential part of a healthy life with roles in ameliorating chronic illnesses and favoring longevity. Nutraceuticals are substances contained in a food or fragment of it influencing health with positive effects on health helping in precenting or treating disorders. We conducted a review illustrating the principal applications of nutraceuticals in autoimmune disorders. Literature reported several studies about exogenous dietary antioxidant supplementation in diverse autoimmune diseases such as rheumatoid arthritis, lupus, diabetes, and multiple sclerosis. In these pathologies, promising results were obtained in some cases. Positive outcomes were generally associated with a reduction of oxidative stress parameters and a boost to antioxidant systems, and sometimes with anti-inflammatory effects. The administration of exogenous substances through food derivates or dietary supplements following scientific standardization was demonstrated to be effective. Further bias-free and extended studies should be conducted that include ever-increasing oxidative stress biomarkers.

Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 De Martinis, Ginaldi, Sirufo, Bassino, De Pietro, Pioggia and Gangemi.)

Although pruritus may sometimes be a consequential situation to neoplasms, it more frequently emerges after commencing chemotherapy. In this review, we present our analysis of the chemotherapy treatments that most often induce skin changes and itching. After discussing conventional chemotherapies capable of inducing pruritus, we present our evaluation of new drugs such as immunological checkpoint inhibitors (ICIs), tyrosine kinase inhibitors, and monoclonal antibodies. Although ICIs and targeted therapy are thought to damage tumor cells, these therapies can modify homeostatic events of the epidermis and dermis, causing the occurrence of cutaneous toxicities in treated subjects. In the face of greater efficacy, greater skin toxicity has been reported for most of these drugs. A remarkable aspect of some reports is the presence of a probable correlation between cutaneous toxicity and treatment effectiveness in tumor patients who were treated with novel drugs such as nivolumab or pembrolizumab. Findings from these experiments demonstrate that the occurrence of any grade of skin side effects can be considered as a predictor of a better outcome. In the near future, studies on the relationship between the onset of skin alterations and outcomes could open new perspectives on the treatment of neoplasms through specific target therapy.

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

The world is now experiencing its third major epidemic of coronavirus (CoV) infections began in Wuhan, Hubei, China, in late 2019 and named COVID-19. After an initial explosive outbreak of pneumonia of unknown etiology in China, the disease spread first to neighboring Asian countries and then worldwide. Patients with COVID-19 presented with a constellation of symptoms such as fever, dry cough, dyspnea, sore throat, and nasal congestion and radiological findings showed bilateral lung glassy opacities. Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death, including physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D supplementation has shown favorable effects in viral infections including influenza and HIV. The effects of vitamin D supplementation during covid 19 infection remain controversial. Looking ahead, clinical studies are needed to define better cut offs for vitamin D levels and, finally, which dosage is the best.

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In BCR - ABL1 -negative MPNs, the driver mutations include JAK 2 , MPL , and CALR . Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.

Background and Objectives: Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories. The aim of this study was to review the role of microRNAs (miRNAs) in CVID, focusing on the involvement of the same miRNAs in various non-infectious clinical complications of CVID, mainly autoimmunity and/or cancer., Materials and Methods: A bibliographic search of the scientific literature was carried out independently by two researchers in scientific databases and search engines. The MeSH terms "microRNAs" and "common variable immunodeficiency" were used. All research articles from inception to May 2020 were considered., Results: The literature data showed the involvement of two miRNAs in primary immunodeficiency: miR-142 and miR-155. Both of these miRNAs have been investigated through mice models, in which miR-142 and miR-155 were deleted. These knock-out (KO) mice models showed phenotypic analogies to CVID patients with hypogammaglobulinemia, adaptive immunodeficiency, polyclonal proliferation, lung disease, and enteric inflammation. miR-142 and miR-155 have been found to be involved in the following autoimmune and neoplastic clinical complications of CVID: Gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, natural killer/Tcell lymphoma (NKTCL), and immune thrombocytopenia., Conclusions: miR-142 and miR-155 deregulation leads to similar CVID phenotypesin KO mice models. Although no data are available on the involvement of these miRNAs in human CVID, their dysregulation has been detected in human CVID comorbidities. The literature data show that miRNA sequences in murine models are comparable to those in humans; therefore, miR-142 and miR-155 involvement in human CVID could be hypothesized.

Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited., Methods: This randomized control trial-ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID ISRCTN15312724-was aimed at comparing the effect of a tele-assisted and in-person intervention based on a behavioral intervention protocol for families with children affected by ASDs. Forty-two parents with children with autism (30 months to 10 years old) were randomly assigned to 12 sessions of an applied behavioral analysis (ABA) intervention implemented in an individual and group setting, either with or without the inclusion of tele-assistance. Pre- and postintervention assessments were conducted using the Home Situation Questionnaire (HSQ-ASD) and the Parental Stress Index (PSI/SF)., Results: Substantial improvements in the perception and management of children's behavior by parents, as well as in the influence of a reduction in parent stress levels on said children's behavior through the use of a tele-assisted intervention, were obtained., Conclusions: This randomized controlled trial demonstrates the evidence-based potential for telehealth to improve treatment of ASDs.

Autism spectrum disorders (ASDs) constitute a set of heterogeneous neurodevelopmental conditions, characterized by a wide genetic variability that has led to hypothesize a polygenic origin. The metabolic profiles of patients with ASD suggest a possible implication of mitochondrial pathways. Although different physiological and biochemical studies reported deficits in mitochondrial oxidative phosphorylation in subjects with ASD, the role of mitochondrial DNA variations has remained relatively unexplored. In this review, we report and discuss very recent evidence to demonstrate the key role of mitochondrial disorders in the development of ASD.

In our study, we explored the construct of alexithymia in parents of children with and without ASD using a multi-method approach based on self-rated and external rater assessment. We also assessed the level of self-report measures of negative affect states such as trait anxiety and depression, and investigated the correlation between the alexithymia construct, trait anxiety, and depression within the broader autism phenotype (BAP). A total sample of 100 parents (25 mothers and 25 fathers in each group) were administered the TAS-20 and the TSIA to measure self-reported and observer-rated alexithymia traits, as well as self-report measures of anxiety and depression. Study results showed that the TSIA but not the TAS-20 was able to detect significant group differences in alexithymia traits among parents of children with and without ASD, with parents of ASD children displaying significantly higher levels of alexithymia. Furthermore, differently from the TAS-20, no significant correlations between the TSIA and measures of anxiety and depression were detected. Taken together, our results suggest the importance of using multi-method approaches to control for potential measurement bias and to detect psychological constructs such as alexithymia in subclinical samples such as parents of children with ASD.

Systemic sclerosis (SSc) is a rare chronic autoimmune disease associated with significant morbidity and mortality. Two main subsets of SSc are recognized: (i) diffuse cutaneous SSc with rapidly progressive fibrosis of the skin, lungs, and other internal organs; and (ii) limited cutaneous SSc, which is dominated by vascular manifestations, with skin and organ fibrosis generally limited and slowly progressing. In spite of intense investigation, both etiology and pathogenesis of SSc are still unknown. Genetic and environmental factors, as well as abnormalities of immune functions, are strongly suggested for etiology, while microvascular abnormalities, immune system activation, and oxidative stress are suggested for the pathogenesis. Recently, it has been found that a multitude of mediators and cytokines are implicated in the fibrotic processes observed in SSc. Among these, a central role could be exerted by "alarmins", endogenous and constitutively expressed proteins/peptides that function as an intercellular signal defense. This review describes, in a detailed manner, the role of alarmins in the pathogenesis of scleroderma.

In late December 2019, a new infectious viral disease appeared. A new betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), has been recognized as the pathogen responsible for this infection. Patients affected by tumors are more vulnerable to infection owing to poor health status, concomitant chronic diseases, and immunosuppressive conditions provoked by both the cancer and antitumor therapies. In this review, we have analyzed some lesser known aspects of the relationship between neoplasms and SARS-CoV-2 infection, starting from the different expression of the ACE2 receptor of the virus in the various neoplastic pathologies, and the roles that different cytokine patterns could have in vulnerability to infection and the appearance of complications. This review also reports the rationale for a possible use of drugs commonly employed in neoplastic therapy, such as bevacizumab, ibrutinib, selinexor, thalidomide, carfilzomib, and PD-1 inhibitors, for the treatment of SARS-CoV-2 infection. Finally, we have highlighted some diagnostic challenges in the recognition of SARS-CoV-2 infection in cancer-infected patients. The combination of these two health problems-tumors and a pandemic virus-could become a catastrophe if not correctly handled. Careful and judicious management of cancer patients with SARS-Cov-2 could support a better outcome for these patients during the current pandemic.

Alternative treatments for neoplastic diseases with new drugs are necessary because the clinical effectiveness of chemotherapy is often reduced by collateral effects. Several natural substances of plant origin have been demonstrated to be successful in the prevention and treatment of numerous tumors. Rosmarinus officinalis L. is a herb that is cultivated in diverse areas of the world. There is increasing attention being directed towards the pharmaceutical capacities of rosemary, utilized for its anti-inflammatory, anti-infective or anticancer action. The antitumor effect of rosemary has been related to diverse mechanisms, such as the antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response and anti-inflammatory response, modification of specific metabolic pathways, and increased expression of onco-suppressor genes. In this review, we aim to report the results of preclinical studies dealing with the anticancer effects of rosemary, the molecular mechanisms related to these actions, and the interactions between rosemary and anticancer drugs. The prospect of utilizing rosemary as an agent in the treatment of different neoplastic diseases is discussed. However, although the use of rosemary in the therapy of neoplasms constitutes a fascinating field of study, large and controlled studies must be conducted to definitively clarify the real impact of this substance in clinical practice., Competing Interests: The authors declare no conflict of interest.

This study is a randomized control trial aimed at testing the role of a human-assisted social robot as an intervention mediator in a socio-emotional understanding protocol for children with autism spectrum disorders (ASD). Fourteen children (4-8 years old) were randomly assigned to 10 sessions of a cognitive behavioural therapy (CBT) intervention implemented in a group setting either with or without the assistance of a social robot. The CBT protocol was based on Rational Emotive Behaviour Therapy (REBT) principles. Pre- and post-intervention assessments were conducted using the Test of Emotional Comprehension (TEC) and the Emotional Lexicon Test (ELT). Substantial improvements in contextualized emotion recognition, comprehension and emotional perspective-taking through the use of human-assisted social robots were attained.

Background: Deficits in working memory tasks have been widely documented in Attention Deficit Hyperactivity Disorder (ADHD) studies. The aim of this study is to evaluate the effects of working memory load in impulsivity during decision-making processes. A delayed discounting (DD) paradigm was used, comparing children with ADHD and age-matched controls., Method: Thirty-two children equally divided between typically developing and ADHD, from 8 to 10 years of age were assigned to sessions of a dual-task paradigm. In the primary task the child has to choose between two different amounts of money at different time delays, while in the secondary task the child has to repeat a random series of digits with different lengths. The experiment was conducted in a school setting., Results: Compared to peers with typical development, delayed discounting was significantly stronger in children with ADHD and discounting rates increased in both groups for heavier memory loads. Furthermore, the memory load impact on frequency of immediate rewards was stronger in children with ADHD compared to typically developing children., Discussion: Results are discussed in terms of the relation between working memory load and decision-making processes, their impact on impulsive behaviour in ADHD and the need for future research to understand possible neurocognitive correlates and use that information to develop better inclusive policies.

Ultraviolet radiation is one of the most pervasive environmental interactions with humans. Chronic ultraviolet irradiation increases the danger of skin carcinogenesis. Probably, oxidative stress is the most important mechanism by which ultraviolet radiation implements its damaging effects on normal cells. However, notwithstanding the data referring to the negative effects exerted by light radiation and oxidative stress on carcinogenesis, both factors are used in the treatment of skin cancer. Photodynamic therapy (PDT) consists of the administration of a photosensitiser, which undergoes excitation after suitable irradiation emitted from a light source and generates reactive oxygen species. Oxidative stress causes a condition in which cellular components, including DNA, proteins, and lipids, are oxidised and injured. Antitumor effects result from the combination of direct tumour cell photodamage, the destruction of tumour vasculature and the activation of an immune response. In this review, we report the data present in literature dealing with the main signalling molecular pathways modified by oxidative stress after photodynamic therapy to target skin cancer cells. Moreover, we describe the progress made in the design of anti-skin cancer photosensitisers, and the new possibilities of increasing the efficacy of PDT via the use of molecules capable of developing a synergistic antineoplastic action.

Background and Objective: Early onset ataxias (EOAs) are a heterogeneous group of neurological conditions, responsible for severe motor disability in paediatric age, which still lack reliable outcome measures. Available scales to assess ataxia, such as the Scale for Assessment and Rating of Ataxia (SARA), are based on subjective assessment of specific motor and language tasks by an examiner, and therefore is age dependent and lacks accuracy in detecting small variations in disease severity. In last years, novel technologies, including computer interfaces and videogames, have emerged for clinical applications and the advent of Internet of Medical Things and of Information Communication Technology have allowed the remote control of such technologies. This pilot study describes a newly developed tool (SaraHome) for the assessment at home of EOA evaluating its feasibility and acceptability on a small sample of children., Methods: Ten EOA children and ten caregivers have been enrolled for a preliminary outpatient evaluation. The Microsoft Kinect 2.0 and Leap Motion Controller (LMC) connected to a personal computer with an ad hoc software have been set-up, for the acquisition of standardized motor tasks performed by the patients with the caregivers' assistance. Acceptance and practicability have been tested by QUEST 2.0 and IMI questionnaires in caregivers and patients respectively., Results: The SaraHome software was developed, based on a collection of services provided by a complex architecture that consists of a Restful interface, which enables to access a series of plugins for the execution of different tasks. A graphical user interface allows the acquisition of the patient movements while performing a motor task. A protocol of standard tasks inspired by SARA was established, and a system of video-assisted instruction provided. The set-up for the optimal acquisition of such protocol by Kinect and LMC has been defined. Both patients and caregivers accomplished the SaraHome assessment with good feedback at the technology acceptance questionnaires., Conclusions: SaraHome represents a newly developed tool for the assessment of ataxia in patients, resulting from the integration of low-cost and easy-accessible technologies. This pilot application highlighted the feasibility and the acceptability of the system, suggesting the potential use in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The human microbiota is made up of the fungi, bacteria, protozoa and viruses cohabiting within the human body. An altered microbiota can provoke diseases such as cancer. The mechanisms by which a modified microbiota can intervene in the onset and progression of neoplastic diseases are manifold. For instance, these include the effects on the immune system and the onset of obesity. A different mechanism seems to be constituted by the continuous and bidirectional relationships existing between microbiota and miRNAs. MiRNAs emerged as a novel group of small endogenous non-coding RNAs from that control gene expression. Several works seem to confirm the presence of a close connection between microbiota and miRNAs. Although the main literature data concern the correlations between microbiota, miRNAs and colon cancer, several researches have revealed the presence of connections with other types of tumour, including the ovarian tumour, cervical carcinoma, hepatic carcinoma, neoplastic pathologies of the central nervous system and the possible implication of the microbiota-miRNAs system on the response to the treatment of neoplastic pathologies. In this review, we summarise the physiological and pathological functions of the microbiota on cancer onset by governing miRNA production. A better knowledge of the bidirectional relationships existing between microbiota and miRNAs could provide new markers for the diagnosis, staging and monitoring of cancer and seems to be a promising approach for antagomir-guided approaches as therapeutic agents.

Alarmins are endogenous mediators released by cells following insults or cell death to alert the host's innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: "alarmins and osteoporosis", "RAGE and osteoporosis", "HMGB1 and osteoporosis", "IL-1 and osteoporosis", "IL 33 and osteopororsis", "S100s protein and osteoporosis". The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases.

Atopic dermatitis is a common chronic/chronically relapsing inflammatory skin disease, with increasing worldwide prevalence. Etiopathogenesis is complex and multifactorial, with a mix of genetic, immunological and environmental aspects. Like in other chronic inflammatory diseases, oxidative stress plays an important pathogenetic role. We reviewed in vivo research studies on humans about oxidative stress and atopic dermatitis. Although sometimes contrasting, overall, they suggest that oxidative stress may have a significant role in atopic dermatitis, but our understanding is still incomplete, at least concerning in vivo data, because of limitations of available literature. Research consists of 33 papers published in 28 years, was not always performed on large study populations, represents a limited number of countries and ethnicities-not always in proportion to their size-and is scattered over multiple papers that, in the majority of cases, cannot be pooled and/or compared because many biomarkers were studied, in different tissues and with different methods. Further, larger studies appear warranted and necessary to shed more light on this aspect of atopic dermatitis, which is important not only to improve our understanding of this disease, but also for potential clinical and therapeutic implications.

B-cell chronic lymphocytic leukemia (B-CLL) is the main cause of mortality among hematologic diseases in Western nations. B-CLL is correlated with an intense alteration of the immune system. The altered functions of innate immune elements and adaptive immune factors are interconnected in B-CLL and are decisive for its onset, evolution, and therapeutic response. Modifications in the cytokine balance could support the growth of the leukemic clone via a modulation of cellular proliferation and apoptosis, as some cytokines have been reported to be able to affect the life of B-CLL cells in vivo. In this review, we will examine the role played by cytokines in the cellular dynamics of B-CLL patients, interpret the contradictions sometimes present in the literature regarding their action, and evaluate the possibility of manipulating their production in order to intervene in the natural history of the disease.

Adolescence is a stage in life when dramatic physical, cognitive and socio-emotional changes occur. When adolescents grow-up in deprived social environments, the chance of psychophysical well-being severely decreases and problems such as delinquency, substance abuse and mental health issues are much more likely to ensue. Third wave cognitive-behavioral interventions are increasingly becoming the chosen instruments to support psychological intervention for young people and adolescents. In this study, we aim to test the feasibility and the adequacy of the outcome measures of an intervention for adolescents at high psychosocial risk, using a modified Discoverer, Noticer, Advisor and Values (DNA-V) protocol aimed at increasing flexible and positive values. The project was conducted in a school located in a low Socio-Economic Status (SES) and severely deprived district of a metropolitan area in Messina, Italy, with 3 classes from 6th to 8th grade. All parents and teachers allowed participants to take part in the pilot study. However, the participants' willingness to engage in the study was low (1 out of 3 classes). Overall, 13 adolescents (72% of the enrolled class) participated in the pilot and only 2 out of 7 teachers and no parents were available for interviews. In its current form, a full RCT is not considered feasible due to general low motivation showed by the participants. Although the sample size was small, the intervention program showed a statistically significant main effect for students' self-report questionnaire, suggesting that those measures were appropriate. Modifications and additional measures are suggested to increase participants' engagement and to overcome the need for parents and teachers' interviews., (Copyright © 2019 Marino, Crimi, Carrozza, Failla, Sfrazzetto, Chilà, Bianco, Arnao, Tartarisco, Cavallaro, Ruta, Vagni and Pioggia.)

Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an "alarmin" able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and-less frequently-antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones.

Background: The Quantitative Checklist for Autism in Toddlers (Q-CHAT) is parent-report screening questionnaire for detecting threshold and sub-threshold autistic features in toddlers. The Q-CHAT is a dimensional measure normally distributed in the general population sample and is able to differentiate between a group of children with a diagnosis of autism and unselected toddlers. Objectives: We aim to investigate the psychometric properties, score distribution, and external validity of the Q-CHAT in an Italian clinical sample of young children with autism versus children with developmental delay and typically developing children. Method: N = 126 typically developing children (TD), n = 139 children with autism, and n = 50 children presenting developmental delay (DD) were administered the Q-CHAT. Standardized measures of cognitive functions, language, and behaviors were also obtained. Results: The Q-CHAT scores were normally distributed and demonstrated adequate internal consistency and good item to total score correlations. The mean Q-CHAT score in the autism group was significantly higher than those found in the DD sample and TD children. No difference on the mean Q-CHAT score between DD and TD children was found. The accuracy of the Q-CHAT to discriminate between autism and TD was very good. Two different cut-points (27 and 31, respectively) maximized sensitivity and specificity for autism versus TD and DD, respectively. Finally, higher Q-CHAT scores were correlated with lower language and social communication skills. Conclusions: In clinical settings, the Q-CHAT demonstrated good psychometric properties and external validity to discriminate autism children not just from children with typical development but also from children with developmental delay.