Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 μg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4+ T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4+ T-cell counts and therapy compliance. Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4+ T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4+ T-cell numbers over study entry levels as compared to placebo. The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012

Equine-assisted interventions (EAIs) are well-known complementary practices combining physical activity with emotional/cognitive stimulation. They are especially suited for children with autism spectrum disorders (ASD) who need a high degree of physical and psychological enrichment. Even though EAIs have become a common practice, stress responses in horses interacting with individuals that can manifest inappropriate behaviours, such as ASD children, have not been thoroughly investigated. Our multicentre study aimed to investigate behavioural and physiological indices of stress in horses involved in EAI standardised sessions with children with ASD compared to typically developing (TD) children. A controlled within-subject design with repeated measurements involving 19 horses and 38 children was adopted. Stress-related behaviours, heart rate, heart rate variability, and eye temperature were recorded during the riding sessions. Moreover, blood samples were collected from horses before and after each session to monitor changes in blood adrenocorticotropic hormone (ACTH), cortisol, and catecholamines. Results indicate that, in general, stress responses in horses involved in EAIs did not differ as a function of the horse being ridden by children with ASD or TD. A lower sympathetic tone in horses involved in ASD sessions was found, while in the mounting and dismounting phases, horses displayed behavioural signs of stress, independently from children’s behaviour. We conclude that professionals working in EAI should increase their awareness of animal welfare and refine riding practices, taking into account horse’s needs.

Due to the global increase in lifespan, the proportion of people showing cognitive impairment is expected to grow exponentially. As target-specific drugs capable of tackling dementia are lagging behind, the focus of preclinical and clinical research has recently shifted towards natural products. Curcumin, one of the best investigated botanical constituents in the biomedical literature, has been receiving increased interest due to its unique molecular structure, which targets inflammatory and antioxidant pathways. These pathways have been shown to be critical for neurodegenerative disorders such as Alzheimer’s disease and more in general for cognitive decline. Despite the substantial preclinical literature on the potential biomedical effects of curcumin, its relatively low bioavailability, poor water solubility and rapid metabolism/excretion have hampered clinical trials, resulting in mixed and inconclusive findings. In this review, we highlight current knowledge on the potential effects of this natural compound on cognition. Furthermore, we focus on new strategies to overcome current limitations in its use and improve its efficacy, with attention also on gender-driven differences.

A growing body of evidence suggests that regular consumption of natural products might promote healthy aging; however, their mechanisms of action are still unclear. Rosmarinic acid (RA) is a polyphenol holding anti-inflammatory, antioxidant and neuroprotective properties. The aim of this study was to characterise the efficacy of an oral administration of RA in promoting healthspan in a mouse model of physiological aging. Aged C57Bl/6 male and female (24-month-old) mice were either administered with RA (500 mg/Kg) or a vehicle in drinking bottles for 52 days while 3-month-old mice receiving the same treatment were used as controls. All subjects were assessed for cognitive abilities in the Morris water maze (MWM) and for emotionality in the elevated-plus maze test (EPM). Brain-derived Neurotrophic Factor (BDNF) protein levels were evaluated in the hippocampus. Since the interaction between metabolic signals and cerebral functions plays a pivotal role in the etiopathogenesis of cognitive decline, the glycaemic and lipid profiles of the mice were also assessed. RA enhanced learning and memory in 24-month-old mice, an effect that was associated to improved glucose homeostasis. By contrast, the lipid profile was disrupted in young adults. This effect was associated with worse glycaemic control in males and with reduced BDNF levels in females, suggesting powerful sex-dependent effects and raising a note of caution for RA administration in young healthy adult subjects.

Equine-assisted activities (EAAs) are considered a suitable innovative rehabilitative practice for children with neurodevelopmental disorders, including autism spectrum disorder (ASD). While standardized scales have been previously used as a tool to evaluate the effects of EAAs on different domains of functioning in ASD children, few studies have considered an ethological approach as a means to describe human–horse interactions in the context of ASD. In this study, we aimed to evaluate the behavior of 19 children with ASD, in comparison with 19 typically developing children (TD), during EAA sessions. We developed an ethogram from the video recordings to assess spatial relationships, social interactions, and communicative behaviors displayed by the child toward the horse, as well as the occurrence of problem behaviors. Results indicate that children’s behaviors during EAA sessions are modulated by sex and age, while previous children’s experience with EAAs appeared to improve interpersonal distance and horse handling. Results from this study highlight the importance of exploring children’s behavioral responses during animal-assisted activities through direct measurements. This may allow linking the quality/strength of the child–horse relationship to the benefits obtained by the child, particularly in the social/communicative domain, a core symptom of ASD.

Background: The role of physical activity (PA) in addressing mental health issues across the lifespan is expanding. Although the focus is primarily on the adult population, this underestimates the potential implementation of these complementary interventions in children and adolescents. Aim: We synthesize the outcomes of umbrella reviews addressing the effectiveness of structured PA on young people’s mental health. Methods: We searched the literature following the PRISMA-ScR methodology for systematic searches consulting the electronic databases of Pubmed, Cochrane Reviews Library, PsycINFO, and PsycArticles, with pre-established eligibility criteria. Results: We included 13 umbrella reviews, published from 2011 to 2023, comprising 91 systematic and meta-analytic reviews. Exercise is the most frequent form of PA (11/13), followed by sports (4/13), dance (3/13), and yoga (1/13). The most consistent positive effects of PA in this portion of the population concerned depressive symptoms, followed by anxiety symptoms. Promising effects were reported for attention, hyperactivity, and impulsivity. Other mental health-related outcomes that emerged as positively influenced by PA concern suicidal ideation, self-esteem, and social functioning, with positive effects of exercise and sport. Conclusions: We suggest that structured PA has promising effects on youth’s mental health although more evidence needs to be gathered. Indeed, although most of the umbrella reviews were of high quality, some methodological weaknesses of primary studies were noted, such as the large data heterogeneity, which, if not adequately addressed, can lead to results that underestimate the complexity of applying PA in clinical practice. Future RCT studies are needed to verify the effectiveness of rigorous PA programs on selected psychopathologies, allowing to expand the current evidence-based recommendations and guidelines, tailoring interventions comprising sport and physical activity to the specific needs of youth.