Clinical Efficacy and Metabolomics Modifications Induced by Polyphenol Compound Supplementation in the Treatment of Residual Dizziness following Semont Maneuver in Benign Paroxysmal Positional Vertigo (BPPV) of the Posterior Semicircular Canal (PSC): Preliminary Results.

Benign paroxysmal positional vertigo (BPPV) represents the most frequent cause of peripheral vertigo. In most cases, it is successfully treated using the canalith repositioning procedure, but it is often followed by continuous lightheadedness in the absence of vertigo or nystagmus (residual dizziness, RD). Our aim is to describe the clinical effectiveness and the urine metabolomics profile of treating these patients with polyphenol compound supplementation. We enrolled 30 patients reporting RD after BPPV of the posterior semicircular canal (PSC) successfully treated using the Semont maneuver. Supplementation with a polyphenol compound was administered for 60 days, and patients were evaluated after 30 and 60 days of treatment using self-administered questionnaires (Visual Analog Scales for Dizziness and Nausea, Dizziness Handicap Inventory, DHI) and urine metabolomics analysis performed using 1H-NMR spectroscopy and multivariate followed by univariate analysis. Most patients reported excellent or good efficacy in the treatment of RD with a significant decrease in VAS and DHI values. The metabolomics analysis identified six significant metabolites related to the treatment, namely 1-methylnicotinamide, anserine, hippurate, lysine, methyl succinate and urea, indicating the inflammatory activities and antioxidant properties of the polyphenol compound. These preliminary data suggest that supplementation with a polyphenol compound could induce some metabolic changes that can help in recovery from RD. However, future steps will require confirmation with a more significant cohort of patients and an extension of the metabolomics evaluation to other problems concerning the different clinical aspects of BPPV, such as the high rate of relapse.

Humoral responses to wild type and ancient BA.1 SARS-CoV-2 variant after heterologous priming vaccination with ChAdOx1 nCoV-19 and BNT162b2 booster dose.

Several countries have recommended a booster dose of Pfizer BNT162b2 vaccine for subjects under the age of 60, who have already received the first dose of ChAdOx1. This is due to several ChAdOx1 vaccine-associated adverse vascular events and thrombocytopenia. Neutralization assay and quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG) were conducted to investigate the long-term responses to vaccine treatment in a cohort of Sardinian participants, who have received heterologous Prime-Boost Vaccination via ChAdOx1 vector vaccine and a booster dose via BNT162b2. The obtained results were compared with those of a cohort of healthcare workers (HCW) who received homologous BNT162b2 (BNT/BNT/BNT) vaccination. One month (T2) and five months after the second and before the third dose (T3), anti-spike antibody or neutralizing titers in the subjects vaccinated with ChAdOx1-S/BNT162b2 were significantly higher than those who experienced the ChAdOx1-S/ChAdOx1-S or BNT162b2/BNT162b2 schedule. These results suggest that a ChAdOx1-S/BNT162b2 regimen provides a more robust antibody response than either of the homologous regimens. However, the anti-spike antibodies or neutralizing titers after the third injection (mRNA vaccine) of ChAdOx1-S as a second dose and BNT162b2 were not statistically different. Homologous and heterologous vaccination provided a strong antibody response. Neutralizing activities were also described against the Omicron BA.1 variant in a sub-group (40) representative of the three vaccination regimens among our cohort.

CDK4/6 inhibition in hormone receptor-positive/HER2-negative breast cancer: Biological and clinical aspects.

A dysregulated cell division, one of the key hallmarks of cancer, results in uncontrolled cellular proliferation. This aberrant process, mediated by a dysregulated cell-cycle machinery and overactivation of cyclin-dependent kinase (CDK) 4 and 6, can potentially promote tumorigenesis. The clinical application of CDK 4/6 inhibitors, developed to inhibit cell-cycle progression, in the treatment regimens of breast cancer (BC) patients is expanding. Currently, three agents, ribociclib, palbociclib, and abemaciclib, are approved for treating patients with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic BC. In addition, abemaciclib is FDA and EMA-approved for patients with hormone receptor-positive HER2-negative, node-positive, early BC at high risk of recurrence. Emerging data suggest potential anti-tumor effects beyond cell cycle arrest, providing novel insights into the agent's mechanisms of action. As a result, a broader application of the CDK4/6 inhibitors in patients with cancer is achieved, contributing to enhanced optimized treatment in the adjuvant and neoadjuvant settings. Herein, the immunomodulatory activities of CDK4/6 inhibitors, their impact on the cell's metabolic state, and the effect on the decision of the cell to undergo quiescence or senescence are discussed. Moreover, this review provides an update on clinical trial outcomes and the differences in the underlying mechanisms between the distinct CDK4/6 inhibitors.

Sardinian Infants of Diabetic Mothers: A Metabolomics Observational Study.

Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance, with hyperglycemia of varying severity with onset during pregnancy. An uncontrolled GDM can lead to an increased risk of morbidity in the fetus and newborn, and an increased risk of obesity or developing type 2 diabetes, hypertension or neurocognitive developmental impairment in adulthood. In this study, we used nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GS-MS) to analyze the urinary metabolomic profile of newborns of diabetic mothers (NDMs) with the aim of identifying biomarkers useful for the monitoring of NDMs and for early diagnosis of predisposition to develop related chronic diseases. A total of 26 newborns were recruited: 21 children of diabetic mothers, comprising 13 in diet therapy (NDM-diet) and 8 in insulin therapy (NDM-insulin), and 5 control children of non-diabetic mothers (CTR). Urine samples were collected at five time points: at birth (T1), on the third day of life (T2), one week (T3), one month (T4) and six months postpartum (T5). At T1, variations were observed in the levels of seven potential biomarkers (acetate, lactate, glycylproline/proline, isocitrate, N,N-dimethylglycine, N-acetylglucosamine and N-carbamoyl-aspartate) in NMD-insulin infants compared to NDM-diet and CTR infants. In particular, the altered metabolites were found to be involved in several metabolic pathways such as citrate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, amino sugar and nucleotide sugar metabolism, and pyruvate metabolism. In contrast, these changes were not visible at subsequent sampling times. The impact of early nutrition (maternal and formula milk) on the metabolomic profile was considered as a potential contributing factor to this finding.

Menopausal transition in multiple sclerosis: relationship with disease activity and brain volume measurements.

Background: Recent evidence has shown a significant association between menopause and multiple sclerosis (MS) progression. This study investigated the possible role of menopause in influencing MS from clinical and neuroradiological perspectives. Notably, the possible association between menopause and brain atrophy has been evaluated. Materials and methods: This study included women with MS whose ages ranged from 45 to 55 years. Demographic and clinical characteristics were collected, and the reproductive phase was defined as non-menopausal or menopausal based on the final menstrual period. Thus, MS activity over the past year was reported as the annualised relapse rate (ARR), and MRI activity (defined as new T2 lesions and/or the presence of gadolinium-enhancing lesions at the last MRI assessment in comparison with the MRI performed within the previous 12 months) were compared between non-menopausal women (non-MW) and menopausal women (MW). Volume measurements of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated using the SIENAX software, and the possible relationship with menopausal status was assessed by regression analysis. Results: The study included 147 women with MS. Eighty-four (57.1%) were MW, with a mean age of 48.5 ± 4.3 years at menopause onset and a mean duration of menopause of 4.1 ± 1.1 years. When compared for ARR, MW reported a lower rate than the non-MW (ARR of 0.29 ± 0.4 vs. 0.52 ± 0.5; p < 0.01). MRI activity was observed in 13.1% of MW and 20.6% of non-MW (p = 0.03). Lower cortical GM volumes (578.1 ± 40.4 mL in MW vs. 596.9 ± 35.8 mL in non-MW; p < 0.01) have also been reported. Finally, multivariate analysis showed a significant association of lower ARR (p = 0.001) and cortical GM volume (p = 0.002) with menopausal status after correction for chronological age and other variables. Discussion: Menopause may be an adverse prognostic factor of MS. Our preliminary results suggest that menopause may facilitate cortical GM atrophy, probably due to a decline in the neuroprotective effects of estrogen, with negative effects on MS evolution.

Right Ventricular Subclinical Dysfunction in SLE Patients Correlates with Metabolomic Fingerprint and Organ Damage.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, and several studies have suggested possible early RV involvement. Aim of the study was to evaluate the 3D echo parameters of the right ventricle (RV) and the metabolomic profile to correlate both with SLE severity. Forty SLE patients, free of cardiovascular disease, were enrolled and the following 3D parameters were evaluated: the RV ejection fraction (RV-EF), longitudinal strain of the interventricular septum (Septal LS), longitudinal strain of the free wall (Free-LS) and the fractional area change (FAC). In addition, a metabolomic analysis was performed. Direct correlations were observed between TAPSE values and the RV 3D parameters. Then, when splitting the population according to the SDI value, it was found that patients with higher cumulative damage (≥3) had significantly lower FAC, RV-EF, Septal LS, and Free-LS values; the latter three parameters showed a significant correlation with the metabolic profile of the patients. Furthermore, the division based on SDI values identified different metabolic profiles related to the degree of RV dysfunction. The RV dysfunction induced by the chronic inflammatory state present in SLE can be identified early by 3D echocardiography. Its severity seems to be related to systemic organ damage and the results associated with a specific metabolic fingerprint constituted by 2,4-dihydroxybutyric acid, 3,4-dihydroxybutyric acid, citric acid, glucose, glutamine, glycine, linoleic acid, oleic acid, phosphate, urea, and valine.

Metabolomic Changes in Patients Affected by Multiple Sclerosis and Treated with Fingolimod.

Current treatment for Multiple Sclerosis (MS) consists of a multidisciplinary approach including disease-modifying therapies. The response to treatment is heterogeneous, representing a crucial challenge in the classification of patients. Metabolomics is an innovative tool that can identifies biomarkers/predictors of treatment response. We aimed to evaluate plasma metabolic changes in a group of naïve Relapsing-Remitting MS patients starting Fingolimod treatment, to find specific metabolomic features that predict the therapeutic response as well as the possible side effects. The study included 42 Relapsing-Remitting MS blood samples, of which 30 were classified as responders after two years of FINGO treatment, whereas 12 patients were Not-Responders. For fifteen patients, samples were collected at four time points: before starting the therapy; at six months after the initiation; at twelve months after; and at twenty-four months after initiation. The serum was analysed through Nuclear Magnetic Resonance and multivariate and univariate statistical analysis. Considering the single comparison between each time point, it was possible to identify a set of metabolites changing their concentrations based on the drug intake. FINGO influences aminoacidic and energy metabolisms and reduces oxidative stress and the activity of the immune system, both typical features of MS.

Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells.

Cancer cells adjust their metabolism to meet energy demands. In particular, glutamine addiction represents a distinctive feature of several types of tumors, including colorectal cancer. In this study, four colorectal cancer cell lines (Caco-2, HCT116, HT29 and SW480) were cultured with or without glutamine. The growth and proliferation rate, colony-forming capacity, apoptosis, cell cycle, redox homeostasis and metabolomic analysis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, high-performance liquid chromatography and gas chromatography/mass spectrometry techniques. The results show that glutamine represents an important metabolite for cell growth and that its deprivation reduces the proliferation of colorectal cancer cells. Glutamine depletion induces cell death and cell cycle arrest in the GO/G1 phase by modulating energy metabolism, the amino acid content and antioxidant defenses. Moreover, the combined glutamine starvation with the glycolysis inhibitor 2-deoxy-D-glucose exerted a stronger cytotoxic effect. This study offers a strong rationale for targeting glutamine metabolism alone or in combination with glucose metabolism to achieve a therapeutic benefit in the treatment of colon cancer.

Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Analysis in Endometriosis Patients: A Prospective Observational Translational Study.

BACKGROUND: Endometriosis affects women of reproductive age, and its pathogenesis is still unclear. Typically, it overlaps other similar medical and surgical conditions, determining a delay in early diagnosis. Metabolomics allows studying metabolic changes in different physiological or pathological states to discover new potential biomarkers. We used the gas chromatography-mass spectrometer (GC-MS) to explore metabolic alterations in endometriosis to better understand its pathophysiology and find new biomarkers. METHODS: Twenty-two serum samples of patients with symptomatic endometriosis and ten without it were collected and subjected to GC-MS analysis. Multivariate and univariate statistical analyses were performed, followed by pathway analysis. RESULTS: Partial least squares discriminant analysis was performed to determine the differences between the two groups (p = 0.003). Threonic acid, 3-hydroxybutyric acid, and proline increased significantly in endometriosis patients, while alanine and valine decreased. ROC curves were built to test the diagnostic power of metabolites. The pathway analysis identified the synthesis and degradation of ketone bodies and the biosynthesis of phenylalanine, tyrosine, and tryptophan as the most altered pathways. CONCLUSIONS: The metabolomic approach identifies metabolic alterations in women with endometriosis. These findings may improve our understanding of the pathophysiological mechanisms of disease and the discovery of new biomarkers.

Omics approaches to understanding the efficacy and safety of disease-modifying treatments in multiple sclerosis.

From the perspective of precision medicine, the challenge for the future is to improve the accuracy of diagnosis, prognosis, and prediction of therapeutic responses through the identification of biomarkers. In this framework, the omics sciences (genomics, transcriptomics, proteomics, and metabolomics) and their combined use represent innovative approaches for the exploration of the complexity and heterogeneity of multiple sclerosis (MS). This review examines the evidence currently available on the application of omics sciences to MS, analyses the methods, their limitations, the samples used, and their characteristics, with a particular focus on biomarkers associated with the disease state, exposure to disease-modifying treatments (DMTs), and drug efficacies and safety profiles.

The impact of the secondary infections in ICU patients affected by COVID-19 during three different phases of the SARS-CoV-2 pandemic.

Microbial secondary infections can contribute to an increase in the risk of mortality in COVID-19 patients, particularly in case of severe diseases. In this study, we collected and evaluated the clinical, laboratory and microbiological data of COVID-19 critical ill patients requiring intensive care (ICU) to evaluate the significance and the prognostic value of these parameters. One hundred seventy-eight ICU patients with severe COVID-19, hospitalized at the S. Francesco Hospital of Nuoro (Italy) in the period from March 2020 to May 2021, were enrolled in this study. Clinical data and microbiological results were collected. Blood chemistry parameters, relative to three different time points, were analyzed through multivariate and univariate statistical approaches. Seventy-four percent of the ICU COVID-19 patients had a negative outcome, while 26% had a favorable prognosis. A correlation between the laboratory parameters and days of hospitalization of the patients was observed with significant differences between the two groups. Moreover, Staphylococcus aureus, Enterococcus faecalis, Candida spp, Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently isolated microorganisms from all clinical specimens. Secondary infections play an important role in the clinical outcome. The analysis of the blood chemistry tests was found useful in monitoring the progression of COVID-19.

Sex Hormones as Key Modulators of the Immune Response in Multiple Sclerosis: A Review.

BACKGROUND: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. METHODS: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. RESULTS: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. CONCLUSIONS: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.

Metabolomics analysis of plasma samples of patients with fibromyalgia and electromagnetic sensitivity using GC-MS technique.

Fibromyalgia (FM) is a chronic and systemic condition that causes widespread chronic pain, asthenia, and muscle stiffness, as well as in some cases depression, anxiety, and disorders of the autonomic system. The exact causes that lead to the development of FM are still unknown today. In a percentage of individuals, the symptoms of FM are often triggered and/or exacerbated by proximity to electrical and electromagnetic devices. Plasma metabolomic profile of 54 patients with fibromyalgia and self-reported electromagnetic sensitivity (IEI-EMF) were compared to 23 healthy subjects using gas chromatography-mass spectrometry (GC-MS) coupled with multivariate statistical analysis techniques. Before the GC-MS analysis the plasma samples were extracted with a modified Folch method and then derivatized with methoxamine hydrochloride in pyridine solution and N-trimethylsilyltrifuoroacetamide. The combined analysis allowed to identify a metabolomic profile able of distinguishing IEI-EMF patients and healthy subjects. IEI-EMF patients were therefore characterized by the alteration of 19 metabolites involved in different metabolic pathways such as energy metabolism, muscle, and pathways related to oxidative stress defense and chronic pain. The results obtained in this study complete the metabolomic "picture" previously investigated on the same cohort of IEI-EMF patients with 1H-NMR spectroscopy, placing a further piece for better understanding the pathophysiological mechanisms in patients with IEI-EMF.

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome.

We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers.

Metabolomics in Otorhinolaryngology.

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the "omics" sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all "omics." Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere's disease. In conclusion, metabolomics study indicates a "fil rouge" that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine.

Analysis of the quality of remote working experience: a speech-based approach.

The current pandemic situation has led to an extraordinary increase in remote working activities all over the world. In this paper, we conducted a research study with the aim to investigate the Quality of Remote Working Experience (QRWE) of workers when conducting remote working activities and to analyse its correlation with implicit emotion responses estimated from the speech of video-calls or discussions with people in the same room. We implemented a system that captures the audio when the worker is talking and extracts and stores several speech features. A subjective assessment has been conducted, using this tool, which involved 12 people that were asked to provide feedback on the QRWE and assess their sentiment polarity during their daily remote working hours. ANOVA results suggest that speech features may be potentially observed to infer the QRWE and the sentiment polarity of the speaker. Indeed, we have also found that the perceived QRWE and polarity are strongly related.

Metabolomics and Microbiomics: New Potential Strategies in Chronic Pain Syndrome.

Chronic pain affects almost 20% of the European adult population and it significantly reduces patients' quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.

Beep4Me: Automatic Ticket Validation to Support Fare Clearing and Service Planning.

An integrated transport service fare system, supported by an agreement for ticket revenue sharing among service providers, is an essential component to improve the experience of the users who can find single tickets for the integrated transport services they look for. A challenge is to find a model to share the revenue which all providers agree on. A solution is to adopt data-driven approaches where user-generated data are collected to extract information on the extent each transport service was used. This is consistently used. However, it suffers from incomplete data, as not all users always validate their ticket when checking out or when switching lines. We studied all technologies available to support automatic ticket validation in order to record when the users access and exit each service line. The contributions of this work are the following: we give an in-depth description of the inner workings of this novel approach describing how we take advantage of each technology; we present the developed solution (Beep4Me), which adds new functionalities to an existing mobile ticketing platform; and we describe our testing framework, which includes most cases users might encounter during a trip. Our results demonstrate how it is possible to collect key data related to validations which can be used first for clearing purposes and then for network planning/fleet optimization.

Alterations of the Intestinal Permeability are Reflected by Changes in the Urine Metabolome of Young Autistic Children: Preliminary Results.

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2-12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites-namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.