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Objectives We conducted a cost–benefit analysis of the pediatric National Immunization Program (NIP) in Italy.Methods An economic model evaluated the benefit–cost ratio (BCR) of the Italian pediatric NIP, including 10 pathogens for mandatory vaccines and 4 pathogens for recommended vaccines for children aged 0–10 years from the healthcare-sector and societal perspectives. Separate decision trees were used to model each vaccine-preventable disease (VPD). The 2020 birth cohort (n = 420,084) was followed over their lifetime; the model projected and compared discounted disease cases, life-years, quality-adjusted life-years (QALYs), and costs (2021 euros) with and without immunization (based on current and pre – vaccine era disease incidence estimates, respectively).Results The pediatric NIP was estimated to prevent 1.8 million cases of VPDs and 3,330 deaths, resulting in 45,900 fewer life-years lost and 57,000 fewer QALYs lost. Vaccination costs of €285 million were offset by disease cost savings of €1.6 billion, resulting in a BCR of 5.6 from a societal perspective (BCR = 1.7 from a healthcare-sector perspective). When QALYs gained were valued, the BCR increased to 15.6.Conclusions The benefits of the Italian pediatric NIP, including averted disease-related morbidity, mortality, and associated costs, highlight the value of continued investment in pediatric immunization.

This study examines the allocation of COVID-19 funding for Indigenous Peoples in Canada, Australia, New Zealand, and the United States during the pandemic’s first wave. Indigenous communities, already facing health disparities, systemic discrimination, and historical forces of colonisation, found themselves further vulnerable to the virus. Analysing the funding policies of these countries, we employed a Health Equity Impact Assessment (HEIA) tool and an Indigenous Lens Tool supplement to evaluate potential impacts. Our results identify three major funding equity issues: unique health and service needs, socioeconomic disparities, and limited access to community and culturally safe health services. Despite efforts for equitable funding, a lack of meaningful consultation led to shortcomings, as seen in Canada’s state of emergency declaration and legal disputes in the United States. New Zealand stood out for integrating Māori perspectives, showcasing the importance of consultation. The study calls for a reconciliation-minded path, aligning with Truth and Reconciliation principles, the UN Declaration on the Rights of Indigenous Peoples, and evolving government support. The paper concludes that co-creating equitable funding policies grounded in Indigenous knowledge requires partnership, meaningful consultation, and organisational cultural humility. Even in emergencies, these measures ensure responsiveness and respect for Indigenous self-determination.

Clinical Scenario: Patella dislocation is a common knee injury resulting in decreased function, increased knee pain, and a higher risk of recurrent patella dislocation. Patients with patella instability are treated surgically or conservatively with physical therapy to minimize redislocation risk and restore function. Clinical Question: In individuals with a patella dislocation, how does treatment (conservative therapy versus medial patellofemoral ligament [MPFL] surgery) affect redislocation rates and patient-perceived function? Summary of Key Findings: This critically appraised topic included 3 studies assessing outcomes in individuals with patella instability treated with MPFL surgery or conservative management. Outcomes included comparing redislocation rates and Kujala scale perceived knee function between participant groups. Surgery included MPFL reconstruction (MPFL-R) in 1 randomized controlled trial and 1 prospective controlled trial and MPFL repair in another randomized controlled trial. Conservative treatment included physical therapy and bracing. All 3 studies demonstrated significantly lower redislocation rates in individuals managed with surgery versus conservative treatment. Reported knee function was significantly higher in the MPFL-R group compared with individuals conservatively managed at 2-year follow-up but not at 1 year. No significant difference in knee function was present between individuals receiving MPFL repair or conservative management at a 2-year follow-up. Clinical Bottom Line: There is moderate-level evidence to support a significant decrease in patella redislocation rates in individuals managed with MPFL surgery compared with conservative treatment. The reviewed studies suggest a significant improvement in patient-perceived knee function at 2 years following MPFL-R but no difference at 1 year following MPFL-R or 2 years after MPFL repair. Strength of Recommendations: Grade B evidence supports lower patella redislocation rates with MPFL surgery compared with nonsurgical treatment. Furthermore, this evidence suggests a potential benefit in perceived knee function 2 years after MPFL-R compared with conservative management. [ABSTRACT FROM AUTHOR]

IntroductionThe contribution of Cannabinoid type 1 receptor (CB1) in mitochondrial energy transduction mechanisms and mitochondrial activities awaits deeper investigations. Our study aims to assess the impact of CB1 absence on the mitochondrial compartment in the liver, focusing on both functional aspects and remodeling processes.MethodsWe used CB1−/− and CB1+/+ male mice. Cytochrome C Oxidase activity was determined polarographically. The expression and the activities of separated mitochondrial complexes and supercomplexes were performed by using Blue-Native Page, Western blotting and histochemical staining for in-gel activity. Key players of Mitochondrial Quality Control processes were measured using RT-qPCR and Western blotting. Liver fine sub-cellular ultrastructural features were analyzed by TEM analysis.Results and discussionIn the absence of CB1, several changes in the liver occur, including increased oxidative capacity, reduced complex I activity, enhanced complex IV activity, general upregulation of respiratory supercomplexes, as well as higher levels of oxidative stress. The mitochondria and cellular metabolism may be affected by these changes, increasing the risk of ROS-related damage. CB1−/− mice show upregulation of mitochondrial fusion, fission and biogenesis processes which suggests a dynamic response to the absence of CB1. Furthermore, oxidative stress disturbs mitochondrial proteostasis, initiating the mitochondrial unfolded protein response (UPRmt). We noted heightened levels of pivotal enzymes responsible for maintaining mitochondrial integrity, along with heightened expression of molecular chaperones and transcription factors associated with cellular stress reactions. Additionally, our discoveries demonstrate a synchronized reaction to cellular stress, involving both UPRmt and UPRER pathways.

Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3’-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLγ) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases.

IntroductionSpatial construction is a complex ability involving attention, global/local visual processing, mental representation, visuo-motor coordination and, to varying extent, working memory and executive functions, and verbal abilities. In developmental neuropsychology, little attention has been paid to comprehend whether and to what extent the above cognitive processes are involved in two main spatial construction tasks, that is drawing and block building.MethodWe used path analysis to test shared and specific effects of verbal and spatial working memory, spatial attention, inhibition, verbal abilities (vocabulary and naming), figure disembedding, mental rotation, and visual-motor coordination, as well as of demographics (sex, age and socio-economic status), on two classical drawing (Rey-Osterrieth Complex Figure; ROCF) and block building (Block design; BD) tasks in a sample of 195 typically developing children (age range: 7–11 years).ResultsFigure disembedding and visuo-motor coordination were the only shared predictors of both spatial construction tasks. Moreover, ROCF score was directly related with spatial attention and inhibition, while BD score was directly related with sex, vocabulary, mental rotation and backward spatial working memory.DiscussionThese findings distinguish between abilities involved in spatial construction regardless of the type of task and those specifically related to ROCF or Block Design, thus providing clues relevant to neuropsychological assessment and intervention in children with spatial construction disorders.

The power behavioural system is a neurobehavioral system that motivates a person to acquire and control resources that are important for survival and reproductive success. When activated, its function is to protect or restore the sense of power, influence, or dominance. Repeated experiences of failure in achieving this goal may result in hyperactivation or deactivation of power-oriented behaviours (analogous to the secondary strategies observed with respect to the attachment behavioural system). Gaining a reliable and valid measure of hyperactivation and deactivation of the power system can be important for understanding an individual's responses to different social contexts and, in clinical settings, can help the therapist identify the client's difficulties that may undermine the therapeutic process. In the present study, we developed the Italian version of the Power Behavioural System Scale (PBSS), a self-report measure developed by Shaver et al. (2011) to assess individual differences in hyperactivation and deactivation of the power system. Results indicated an adequate fit to the expected two-factor model, and the measure proved to be reliable and had good convergent and structural validity, allowing the quantification of individual differences in power system hyperactivation and deactivation.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and impaired beta-cell secretory function. Since existing treatments often present side effects based on different mechanisms, alternative therapeutic options are needed. In this scenario, the present study first evaluates the cytotoxicity of decoctions from the leaves, stems, and roots of Cucumis prophetarum L. on HepG2 and L6C5 cells. The extracts were chemically investigated by UV–Vis and ATR-FTIR spectroscopic techniques and by ultra high-performance chromatographic techniques, coupled with high-resolution mass spectrometry. Briefly, decoctions from the leaves and stems were mainly composed of apigenin C-glycosides, while the root decoction was rich in raffinose and cucumegastigmane II. To evaluate the insulin-sensitizing properties of the extracts in insulin-resistant L6 myoblasts, an evaluation by Western blot analysis of the proteins in the insulin signaling pathway was then performed. Particularly, key proteins of insulin signaling were investigated, i.e., insulin receptor substrate (IRS-1), protein kinase B (PKB/AKT), and glycogen synthase kinase-3 (GSK-3β), which have gained considerable attention from scientists for the treatment of diabetes. Under all conditions tested, the three decoctions showed low cytotoxicity. The stem and root decoction (300 μg/mL) resulted in a significant increase in the levels of p-IRS-1 (Tyr612), GSK3β (Ser9), and p-AMPK (Thr172) compared to those of the palmitic acid-treated group, and the leaf decoction resulted an increase in the level of p-IRS-1 (Tyr612) and p-AMPK (Thr172) and a decrease in p-GSK3β (Ser9) compared to the levels for the palmitic acid-treated group. The root decoction also reduced the level of p-mToR (Ser2448). Overall, the acquired data demonstrate the effect of reducing insulin resistance induced by the investigated decoctions, opening new scenarios for the evaluation of these effects aimed at counteracting diabetes and related diseases in animal models.

Background: This study evaluates the therapeutic efficacy of HAr® (a novel ophthalmic solution containing modified hyaluronic acid covalently linked to riboflavin) compared to hyaluronic acid eye drops in patients with dry eye disease (DED). Methods: Sixteen consecutive patients with bilateral medium to severe DED were divided into two groups. Group 1 received HAr® 0.1 % (Ribohyal®), while Group 2 received HA 0.1 % eye drops. Parameters such as Ocular Surface Disease Index (OSDI) score, osmolarity, break-up time (BUT), non-invasive BUT (NIBUT), tear meniscus measurement, Schirmer test, and Oxford Staining were evaluated. This study has been successfully registered on ClinicalTrials.gov public (Identifier NCT06122428) Results: The Ribohyal group showed faster improvement in OSDI scores, with a statistically significant difference at 2 h (mean classification difference: −51.75; p = 0.0003). Photophobia significantly reduced at 2 h, 4 weeks, and 8 weeks in the Ribohyal group compared to baseline (p

This paper aimed at investigating the relationship between HEXACO personality traits and academic performance in two samples of Italian 10–14 years old middle-school adolescents (N = 714 and N = 1093) using Multilevel Mixed Models. The main results show that: 1) Conscientiousness and Openness to Experience were the most important predictors of school performance, followed by Honesty-Humility; 2) a modest effect was present also for eXtraversion and Emotionality; 3) these influences occurred net of the influence of gender and class and could be generalized to male and female adolescents across 6th, 7th and 8th grade; 5) Perfectionism, Diligence and Prudence within Conscientiousness, Inquisitiveness within Openness, and Sincerity within Honesty-Humility were the facets more correlated with school performance; 6) results were replicated in two studies. Results are discussed and conclusions are drawn.

Inconsistent data are available on mental rotation performance in neurotypicals with high autistic-like traits. Here, we tested whether global-local visual processing abilities mediate the influence of specific autistic-like trait domains (social skill, attention switching, attention-to-detail, communication, and imagination) on mental rotation. Neurotypical participants (N = 128) underwent an assessment of autistic-like traits, a flanker task with hierarchical stimuli, and a mental rotation task. Path analysis showed that Reaction Times on the incongruent/local condition of the flanker task mediated the relationship between attention-to-detail and mental rotation accuracy. These findings indicate that a better capacity of ignoring incongruent global information to identify local information (reduced global interference) in persons with high non-social autistic-like traits, as attention-to-detail, facilitates mental rotation performance.

Extreme weather events are increasingly recognized as major stress factors for forest ecosystems, causing both immediate and long-term effects. This study focuses on the impacts experienced by the forests of Valdisotto, Valfurva, and Sondalo (28% of the total area is covered by forests) in Upper Valtellina (Italy) due to the Vaia storm that occurred in October 2018. To define the immediate impacts of Vaia, we assess the economic value of forest ecosystem services (ESs), particularly those provided by timber production and carbon sequestration, pre- and post-Vaia and during the emergency period. We used the market price method to assess the economic values of timber production and carbon sequestration, as these are considered to be marketable goods. Based on data processed from Sentinel-2 satellite images (with a spatial resolution of 10 m), our results show that, despite the reduction in forest area (−2.02%) and timber stock (−2.38%), the economic value of the timber production increased after Vaia due to higher timber prices (i.e., from a total of €124.97 million to €130.72 million). However, considering the whole emergency period (2019–2020), the total losses are equal to €5.10 million for Valdisotto, €0.32 million for Valfurva, and €0.43 million for Sondalo. Instead, an economic loss of 2.88% is experienced for carbon sequestration, with Valdisotto being the more affected municipality (−4.48% of the pre-Vaia economic value). In terms of long-term impacts, we discuss the enhanced impacts due to the spread of the bark beetle Ips typopgraphus.

Abstract Background In spite of past efforts to increase screening uptake, the rates of screening-detectable cancers including breast, cervical, colorectal and lung are rising among Indigenous persons in Ontario compared to other Ontarians. The Ontario Ministry of Health has an equity framework, the Health Equity Impact Assessment (HEIA) Tool, that was developed to guide organizations in the provision of more equitable health and social services. Although the HEIA Tool identifies that the health of Indigenous persons may benefit from more equitable provision of health and social services, it provides very little specific guidance on how to apply the HEIA Tool in a culturally relevant way to policies and programs that may impact Indigenous peoples. Discussion Guided by the Calls to Action from the Truth and Reconciliation Commission of Canada and the United Nations Declaration on the Rights of Indigenous Peoples, an Indigenous Lens Tool was developed through a collaborative and iterative process with stakeholders at Cancer Care Ontario and with representatives from Indigenous community-based organizations. The Indigenous Lens Tool consists of four scenarios, with supporting documentation that provide context for each step of the HEIA Tool and thereby facilitate application of the equity framework to programs and policies. The document is in no way meant to be comprehensive or representative of the diverse health care experiences of Indigenous peoples living in Canada nor the social determinants that surround health and well-being of Indigenous peoples living in Canada. Rather, this document provides a first step to support development of policies and programs that recognize and uphold the rights to health and well-being of Indigenous peoples living in Canada. Conclusions The Indigenous Lens Tool was created to facilitate implementation of an existing health equity framework within Cancer Care Ontario (now Ontario Health). Even though the Indigenous Lens Tool was created for this purpose, the principles contained within it are translatable to other health and social service policy applications.

Abstract The function of dreams is a longstanding scientific research question. Simulation theories of dream function, which are based on the premise that dreams represent evolutionary past selective pressures and fitness improvement through modified states of consciousness, have yet to be tested in cross-cultural populations that include small-scale forager societies. Here, we analyze dream content with cross-cultural comparisons between the BaYaka (Rep. of Congo) and Hadza (Tanzania) foraging groups and Global North populations, to test the hypothesis that dreams in forager groups serve a more effective emotion regulation function due to their strong social norms and high interpersonal support. Using a linear mixed effects model we analyzed 896 dreams from 234 individuals across these populations, recorded using dream diaries. Dream texts were processed into four psychosocial constructs using the Linguistic Inquiry and Word Count (LIWC-22) dictionary. The BaYaka displayed greater community-oriented dream content. Both the BaYaka and Hadza exhibited heightened threat dream content, while, at the same time, the Hadza demonstrated low negative emotions in their dreams. The Global North Nightmare Disorder group had increased negative emotion content, and the Canadian student sample during the COVID-19 pandemic displayed the highest anxiety dream content. In conclusion, this study supports the notion that dreams in non-clinical populations can effectively regulate emotions by linking potential threats with non-fearful contexts, reducing anxiety and negative emotions through emotional release or catharsis. Overall, this work contributes to our understanding of the evolutionary significance of this altered state of consciousness.

In the European Union, salmonellosis is one of the most important zoonoses reported. Poultry meat and egg products are the most common food matrices associated with Salmonella presence. Moreover, wild and domestic animals could represent an important reservoir that could favour the direct and indirect transmission of pathogens to humans. Salmonella spp. can infect carnivorous or omnivorous wild birds that regularly ingest food and water exposed to faecal contamination. Birds kept in captivity can act as reservoirs of Salmonella spp. following ingestion of infected prey or feed. In this paper, we describe the isolation of different Salmonella serovars in several species of raptors hosted in aviaries in an Italian wildlife centre and in the raw chicken necks used as their feed but intended for human consumption. Characterisations of strains were carried out by integrating classical methods and whole genome sequencing analysis. The strains of S. bredeney isolated in poultry meat and birds belonged to the same cluster, with some of them being multidrug-resistant (MDR) and carrying the Col(pHAD28) plasmid-borne qnrB19 (fluoro)quinolone resistance gene, thus confirming the source of infection. Differently, the S. infantis found in feed and raptors were all MDR, carried a plasmid of emerging S. infantis (pESI)-like plasmid and belonged to different clusters, possibly suggesting a long-lasting infection or the presence of additional undetected sources. Due to the high risk of fuelling a reservoir of human pathogens, the control and treatment of feed for captive species are crucial.

BackgroundOverweight/obesity are metabolic disorder resulting from behavioral, environmental, and heritable causes. WHO estimates that 50% of adults and 30% of children and adolescents are overweight or obese, and, in parallel, an ongoing decline in sperm quality and male fertility has been described. Numerous studies demonstrated the intimate association between overweight/obesity and reproductive dysfunction due to a highly intricate network of causes not yet completely understood. This study expands the knowledge on the impact of a short-term high-fat diet (st-HFD) on rat testicular activity, specifically on steroidogenesis and spermatogenesis, focusing on the involved molecular mechanisms related to mitochondrial dynamics, blood-testis barrier (BTB) integrity, and SIRT1/NRF2/MAPKs pathways.MethodsTen adult Male Wistar rats were divided into two groups of five and treated with a standard diet or an HFD for five weeks. At the end of the treatment, rats were anesthetized and sacrificed by decapitation. Blood was collected for serum sex hormone assay; one testis was stored at -80ÅãC for western blot analysis, and the other, was fixed for histological and immunofluorescence analysis.ResultsFive weeks of HFD results in reduced steroidogenesis, increased apoptosis of spermatogenic cells, and altered spermatogenesis, as highlighted by reduced protein levels ofmeiotic and post-meiotic markers. Further, we evidenced the compromission of the BTB integrity, as revealed by the downregulation of structural proteins (N-Cadherin, ZO-1, occludin, connexin 43, and VANGL2) other than the phosphorylation of regulative kinases (Src and FAK). At the molecular level, the impairment of mitochondrial dynamics (fission, fusion, andbiogenesis), and the dysregulation of the SIRT1/NRF2/MAPKs signaling pathways, were evidenced. Interestingly, no change was observed in the levels of pro-inflammatory markers (TNFα, NF-kB, and IL-6).ConclusionsThe combined data led us to confirm that overweight is a less severe state than obesity. Furthermore, understanding the molecular mechanisms behind the association between metabolic disorders and male fertility could improve the possibility of identifying novel targets to prevent and treat fertility disorders related to overweight/obesity.