The Utility of a Computerized Algorithm Based on a Multi-Domain Profile of Measures for the Diagnosis of Attention Deficit/Hyperactivity Disorder

The current gold standard for diagnosis of attention deficit/hyperactivity disorder (ADHD) includes subjective measures, such as clinical interview, observation, and rating scales. The significant heterogeneity of ADHD symptoms represents a challenge for this assessment and could prevent an accurate diagnosis. The aim of this work was to investigate the ability of a multi-domain profile of measures, including blood fatty acid (FA) profiles, neuropsychological measures, and functional measures from near-infrared spectroscopy (fNIRS), to correctly recognize school-aged children with ADHD. To answer this question, we elaborated a supervised machine-learning method to accurately discriminate 22 children with ADHD from 22 children with typical development by means of the proposed profile of measures. To assess the performance of our classifier, we adopted a nested 10-fold cross validation, where the original dataset was split into 10 subsets of equal size, which were used repeatedly for training and testing. Each subset was used once for performance validation. Our method reached a maximum diagnostic accuracy of 81% through the combining of the predictive models trained on neuropsychological, FA profiles, and deoxygenated-hemoglobin features. With respect to the analysis of a single-domain dataset per time, the most discriminant neuropsychological features were measures of vigilance, focused and sustained attention, and cognitive flexibility; the most discriminating blood FAs were linoleic acid and the total amount of polyunsaturated fatty acids. Finally, with respect to the fNIRS data, we found a significant advantage of the deoxygenated-hemoglobin over the oxygenated-hemoglobin data in terms of predictive accuracy. These preliminary findings show the feasibility and applicability of our machine-learning method in correctly identifying children with ADHD based on multi-domain data. The present machine-learning classification approach might be helpful for supporting the clinical practice of diagnosing ADHD, even fostering a computer-aided diagnosis perspective

<i>Leishmania tarentolae</i> as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein

Background: Protozoa of the genus Leishmania are characterized by their capacity to target macrophages and Dendritic Cells (DCs). These microorganisms could thus be exploited for the delivery of antigens to immune cells. Leishmania tarentolae is regarded as a non-pathogenic species; it was previously used as a biofactory for protein production and has been considered as a candidate vaccine or as an antigen delivery platform. However, results on the type of immune polarization determined by L. tarentolae are still inconclusive. Methods: DCs were derived from human monocytes and exposed to live L. tarentolae, using both the non-engineered P10 strain, and the same strain engineered for expression of the spike protein from SARS-CoV-2. We then determined: (i) parasite internalization in the DCs; and (ii) the capacity of the assayed strains to activate DCs and the type of immune polarization. Results: Protozoan parasites from both strains were effectively engulfed by DCs, which displayed a full pattern of maturation, in terms of MHC class II and costimulatory molecule expression. In addition, after parasite infection, a limited release of Th1 cytokines was observed. Conclusions: Our results indicate that L. tarentolae could be used as a vehicle for antigen delivery to DCs and to induce the maturation of these cells. The limited cytokine release suggests L. tarentolae as a neutral vaccine vehicle that could be administered in association with appropriate immune-modulating molecules

Pseudo-Mannosylated DC-SIGN Ligands as Potential Adjuvants for HIV Vaccines

The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs). Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19) to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated

Age level vs grade level for the diagnosis of ADHD and neurodevelopmental disorders

A number of worldwide studies have demonstrated that children born later in the school year are more likely to receive an ADHD diagnosis than their same school-year peers. There is, however, variation in findings between countries. We aimed to confirm whether relative age is associated with ADHD diagnosis, with or without comorbidities, and to investigate whether relative age is associated with ADHD type and severity, and if this age relationship is in common with other neurodevelopmental disorder. We used the Lombardy Region\u2019s ADHD registry. Data on children aged 6\ua0years and older from September 1, 2011 to December 31, 2017 were considered. We calculated incidence ratios to assess the inter-relations between relative age within the school year, using age at diagnosis of ADHD or of other psychiatric disorder, year of diagnosis, and total number of children born in Lombardy during the corresponding timeframe. Data on ADHD type, severity of diagnosed disorder clinical global impressions\u2013severity scale, and repetition of a school-grade were also considered. 4081 children, 2856 of whom with ADHD, were identified. We confirmed that the cumulative incidence of ADHD diagnosis was greatest for younger children, in particular for boys, for whom the prevalence is greater. The relative age effect was not accounted for by ADHD comorbid disorders, ADHD of combined type or severity. The relative age effect was also observed for children with other neurodevelopmental disorders (without ADHD), with a similar profile as ADHD children: the incidence ratio was 1.78 (95% CI 1.07\u20132.97; p < 0.0247) for boys diagnosed before age ten. The findings have a potential implication for diagnostic and therapeutic practice, educational advice, and policies, besides to better plan and organize service systems and appropriately inform parents, children, and citizens

Differences between centers in functional outcome of patients with ADHD after 1 year from the time of diagnosis

Although the pharmacological therapy of ADHD has been widely studied, little has been done to compare the different therapeutic approaches (e.g., drug therapy vs. psychological treatments) and even less has been done to compare the outcome of the therapy between centers. This multicenter observational study aims to assess between-center variation in functional outcome of ADHD patients one year after the diagnosis, according to the treatment received. We used the Regional ADHD Registry data on 1429 patients enrolled in 16 ADHD centers in the 2011-2022 period. To evaluate the effectiveness of the therapy we used a generalized linear mixed model with the center as the random effect, including patient condition at diagnosis and center characteristics, weighting by the inverse of the propensity score of the treatment received by the patient. Between-center variation was expressed as the relative difference in odds-ratios between the observed and the expected number of patients whose condition improved, using the Clinical Global Impressions-Improvement Scale (CGI-I), and the relative 95% CI. Patients who received combined treatment were significantly more likely to improve compared to other treatment groups (65.5% vs 54.4% for methylphenidate alone, 53.4% for psychological treatment alone, or 40.5% for no therapy). Adjusted for patients and center characteristics, the log-odds ratio ranged from 0.85 (0.29-1.55 95% CI) to -0.64 (-1.17-0.18 95% CI). The mean expected probability of improvement after one year of therapy for an average patient with ADHD for each center was 47.7% in a center at the 25th percentile and 61.2% in a center at the 75th percentile of the outcome distribution after adjustments. The wide between-center variation in patient functional improvement one year after the diagnosis of ADHD could be largely explained by center-specific therapeutic approaches or attitudes. More careful and stringent work is needed to reduce differences in responses between centers, as could formal and periodic audit programs within and between centers