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SARS-CoV-2 infection shows a wide-ranging clinical severity, requiring prognostic markers. We focused on S100B, a calcium-binding protein present in biological fluids, being a reliable biomarker in disorders having inflammatory processes as common basis and RAGE as main receptor. Since Covid-19 is characterized by a potent inflammatory response also involving RAGE, we tested if S100B serum levels were related to disease severity. Serum samples (n = 74) were collected from hospitalized SARS-CoV-2 positive patients admitted to Covid center. Illness severity was established by admission clinical criteria and Covid risk score. Treatment protocols followed WHO guidelines available at the time. Circulating S100B was determined by ELISA assay. Statistical analysis used Pearson’s χ 2 test, t-Test, and ANOVA, ANCOVA, Linear Regression. S100B was detected in serum from Covid-19 patients, significantly correlating with disease severity as shown both by the level of intensity of care ( p  < 0.006) as well by the value of Covid score (Multiple R-squared: 0.3751); the correlation between Covid-Score and S100B was 0.61 ( p  < 0.01). S100B concentration was associated with inflammation markers (Ferritin, C-Reactive Protein, Procalcitonin), and organ damage markers (Alanine Aminotransferase, Creatinine). Serum S100B plays a role in Covid-19 and can represent a marker of clinical severity in Sars-CoV-2 infected patients.

Multidrug-resistant (MDR) organisms are emerging as some of the main healthcare problems worldwide. During the COVID-19 pandemic, several Infection Prevention and Control (IPC) measures have been adopted to reduce nosocomial microorganism transmission. We performed a case–control study to identify if the incidence of MDR bacterial infections while using pandemic-related preventive measures is lower than in previous years. From 2017 to 2020, we monitored hospital discharges over a four-month period (P #) (1 March to 30 June) in St. Andrea Hospital, Rome. In total, we reported 1617 discharges. Pearson’s chi-squared test was used to identify significant differences. A value of p ≤ 0.05 was considered statistically significant. A significant reduction in the incidence of total MDR bacterial infections was observed during the pandemic compared to in prepandemic years (p < 0.05). We also found a significantly higher incidence of MDR bacterial infections in COVID-19 departments compared with other medical departments (29% and 19%, respectively), with extended-spectrum β-lactamase Klebsiella pneumoniae as the pathogens presenting the highest increase. This study demonstrates that maintaining a high level of preventive measures could help tackle an important health problem such as that of the spread of MDR bacteria.

Migraine is the most disabling and expensive chronic disorders, the etiology of which is still not fully known. The neuronal systems, (glutammatergic, dopaminergic, serotoninergic and GABA-ergic) whose functionality is partly attributable to genetically determined factors, has been suggested to play an important role. The treatment of acute attacks and the prophylactic management of chronic forms include the use of different category of drugs, and it is demonstrated that not each subject has the same clinical answer to them. The reason of this is to be searched in different functional capacity and quantity of phase I enzymes (such as different isoforms of CYP P450), phase II enzymes (such as UDP-glucuronosyltransferases), receptors (such as OPRM1 for opioids) and transporters (such as ABCB1) involved in the metabolic destiny of each drug, all of these dictated by DNA and RNA variations. The general picture is further exacerbated by the need for polytherapies, often also to treat comorbidities, which may interfere with the pharmacological action of anti-migraine drugs. Personalized medicine has the objective of setting the optimal therapies in the light of the functional biochemical asset and of the comorbidities of the individual patient, in order to obtain the best clinical response. Novel therapeutic perspectives in migraine includes biotechnological drugs directed against molecules (such as CGRP and its receptor) that cause vasodilatation at the peripheral level of the meningeal blood vessels and reflex stimulation of the parasympathetic system. Drug-drug interactions and the possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale. Drug-drug interactions and their possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale.

The COVID-19/SARS-CoV-2 pandemic struck health, social and economic systems worldwide, and represents an open challenge for scientists —coping with the high inter-individual variability of COVID-19, and for policy makers —coping with the responsibility to understand environmental factors affecting its severity across different geographical areas. Air pollution has been warned of as a modifiable factor contributing to differential SARS-CoV-2 spread but the biological mechanisms underlying the phenomenon are still unknown. Air quality and COVID-19 epidemiological data from 110 Italian provinces were studied by correlation analysis, to evaluate the association between particulate matter (PM)2.5 concentrations and incidence, mortality rate and case fatality risk of COVID-19 in the period 20 February–31 March 2020. Bioinformatic analysis of the DNA sequence encoding the SARS-CoV-2 cell receptor angiotensin-converting enzyme 2 (ACE-2) was performed to identify consensus motifs for transcription factors mediating cellular response to pollutant insult. Positive correlations between PM2.5 levels and the incidence (r = 0.67, p < 0.0001), the mortality rate (r = 0.65, p < 0.0001) and the case fatality rate (r = 0.7, p < 0.0001) of COVID-19 were found. The bioinformatic analysis of the ACE-2 gene identified nine putative consensus motifs for the aryl hydrocarbon receptor (AHR). Our results confirm the supposed link between air pollution and the rate and outcome of SARS-CoV-2 infection and support the hypothesis that pollution-induced over-expression of ACE-2 on human airways may favor SARS-CoV-2 infectivity.

Background Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25–30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment. Methods Pre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann–Whitney test. Results Twenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (< 3 months) to nivolumab treatment. The median value of kyn/trp ratio was 0.06 µg/ml and the median value of quinolinic acid was 68.45 ng/ml. A significant correlation between early progression and higher kyn/trp ratio and quinolinic acid concentration was observed ( p  = 0.017 and p  = 0.005, respectively). Patients presenting lower values of kyn/trp ratio and quinolinic acid levels showed longer PFS (median PFS not reached versus 3 months; HR: 0.3; p  = 0.018) and OS (median OS not reached vs 3 months; HR: 0.18; p  = 0.0005). Conclusion IDO activity, expressed as kyn/trp ratio, is associated with response to immunotherapy; in particular, higher kyn/trp ratio could predict resistance to anti-PD-1 treatment. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in those patients with high level of kyn/trp ratio.

Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a welltolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-KB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-κB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.

Introduction This systematic review explores the hypothesis that various lipid categories and lipid metabolism-related genomic variations link to mental disorders, seeking potential clinically useful markers. Methods We searched PubMed, Scopus, and PsycInfo databases until October 12th, 2024, using terms related to lipidomics, lipid-related genomics, and different mental disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia (SCZ), and Obsessive–Compulsive Disorder (OCD). Eligible studies were assessed. Extracted data included author, year, methodology, outcomes, genes, and lipids linked to disorders. Bias and evidence certainty were evaluated. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and a registered protocol (PROSPERO: CRD42023438862). Results A total of 27 studies were included. SCZ showed alterations in 77 lipids, including triglycerides (TG), ceramides, and phosphatidylcholine, while MDD and BD exhibited 97 and 47 altered lipids, respectively, with overlap among disorders. Shared genes, such as ABCA13, DGKZ, and FADS, and pathways involving inflammation, lipid metabolism, and mitochondrial function were identified. OCD was associated with sphingolipid signaling and peroxisomal metabolism. Discussion Lipid signatures in MDD, BD, and SCZ shed light on underlying processes. Further research is needed to validate biomarkers and refine their clinical applications in precision psychiatry. Highlights Various lipid categories can link to mental disorders, being potential clinically useful markers. This systematic review comprehensively analyzed the role of lipidomics and lipid-related genomics in Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia (SCZ), and Obsessive-Compulsive Disorder (OCD). Specific lipid signatures, such as polyunsaturated fatty acids, high-density lipoproteins (HDL), and arachidonic acid, shed light on the underlying biological processes in MDD, BD, and SCZ. Advancing lipidomics research may pave the way for precision psychiatry, enabling personalized diagnostic and therapeutic strategies for mental disorders.

Background This study investigates the role of genetic variations in the 5-Hydroxytryptamine Receptor 2A ( HTR2A ) gene in subjects with treatment-resistant obsessive–compulsive disorder (TR-OCD), compared to individuals with other treatment-resistant mental disorders (TRMDs). The goal is to explore whether specific HTR2A polymorphisms contribute to distinguishing TR-OCD from other TRMDs, thereby advancing our understanding of the underlying pathophysiological mechanisms. Methods A retrospective observational study was conducted with 210 individuals affected by TRMDs (72 with major depressive disorder, 62 with bipolar disorder, 37 with schizophrenia, 30 with OCD, and 9 with other diagnoses). Genetic analyses focused on three HTR2A single nucleotide polymorphisms (SNPs) (rs6314, rs7997012, and rs6311), using next-generation sequencing from blood samples. Chi-square testing and single- and multiple-SNP analyses were employed to study the association between these SNPs and the TR-OCD diagnosis. Results The analysis revealed that the HTR2A rs7997012 A|A vs. G|G genotype was significantly associated with a higher likelihood of belonging to the TR-OCD group compared to other TRMDs, with an odds ratio of 6.85 (95% CI = 2.44–19.26; p  < 0.001). The same genotype, compared to the combined G|G and A|G genotypes, showed a significant association with TR-OCD (OR = 7.68; 95% CI = 2.90–20.34; p  < 0.001). Haplotype analyses demonstrated a significant global association between the combined rs6314-rs7997012-rs6311 variants and TR-OCD ( p  = 0.028). Specifically, the G-G-C haplotype was significantly associated with a reduced likelihood of TR-OCD (OR = 0.32; 95% CI = 0.11–0.93; p  = 0.038) compared to the reference haplotype G-G-T. Conclusions This preliminary study identifies the rs7997012 polymorphism in the HTR2A gene as a potential genetic marker for TR-OCD, distinguishing it from other TRMDs. The study of rs7997012 and other genetic variants within the serotonergic system may enhance our understandings of the biological mechanisms underlying OCD and contribute to the development of precision psychiatry approaches.

Clinical trials showed that only a subset of patients benefits from immunotherapy, suggesting the need to identify new predictive biomarker of resistance. Indoleamine-2,3-dioxygenase (IDO) has been proposed as a mechanism of resistance to anti-PD-1 treatment, and serum kynurenine/tryptophan (kyn/trp) ratio represents a possible marker of IDO activity. Metastatic non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and head and neck squamous cell carcinoma (HNSCC) treated with nivolumab as second-line treatment were included in this prospective study. Baseline serum kyn and trp levels were measured by high-performance liquid chromatography to define the kyn/trp ratio. The χ -test and -test were applied to compare frequencies and mean values of kyn/trp ratio between subgroups with distinct clinical/pathological features, respectively. Median baseline kyn/trp ratio was defined and used as cutoff in order to stratify the patients. The association between kyn/trp ratio, clinical/pathological characteristics, response, progression-free survival (PFS), and overall survival (OS) was analyzed. Fifty-five patients were included. Mean baseline serum kyn/trp ratio was significantly lower in female than in male patients (0.048 vs. 0.059, respectively, = 0.044) and in patients with lung metastasis than in others (0.053 vs. 0.080, respectively, = 0.017). Mean baseline serum kyn/trp ratio was significantly higher in early progressor patients with both squamous and non-squamous NSCLC ( = 0.003) and with a squamous histology cancer (19 squamous NSCLC and 14 HNSCC, = 0.029). The median value of kyn/trp ratio was 0.06 in the overall population. With the use of median value as cutoff, patients with kyn/trp ratio > 0.06 had a higher risk to develop an early progression (within 3 months) to nivolumab with a trend toward significance ( = 0.064 at multivariate analysis). Patients presenting a baseline kyn/trp ratio ≤0.06 showed a longer PFS [median 8 vs. 3 months; hazard ratio (HR): 0.49; 95% confidence interval (CI) 0.24-1.02; = 0.058] and a significantly better OS than did those with a kyn/trp ratio > 0.06 (median 16 vs. 4 months; HR: 0.39; 95% CI 0.19-0.82; = 0.013). Serum kyn/trp ratio could have both prognostic and predictive values in patients with solid tumor treated with immunotherapy, probably reflecting a primary immune-resistant mechanism regardless of the primary tumor histology. Its relative weight is significantly related to gender, site of metastasis, NSCLC, and squamous histology, although these suggestive data need to be confirmed in larger studies.

Mental disorders affect nearly one billion persons worldwide, having a substantial burden on individuals, families, and healthcare systems. Current diagnostic and therapeutic approaches could fail to reach optimal outcomes, highlighting the need for more effective and personalized interventions. Precision psychiatry aims to address this challenge by integrating multidimensional data, ranging from genomics and epigenomics to neuroimaging and psychometric assessments, through advanced computational tools such as machine learning and artificial intelligence. This transdisciplinary approach could allow the study of biologically informed endophenotypes, improve diagnostic accuracy, and support individualized treatment strategies. Emerging technologies, including pharmaco-neuroimaging, virtual histology, and large-scale consortia, are advancing the field by elucidating the molecular and circuit-level correlates of mental disorders. Although significant progress has been made, the translational gap between research and clinical practice remains a critical issue. Effective implementation will require the systematic integration of bioinformatic tools, big data analytics, and clinician-guided interpretation, in a context in which the evolving landscape of precision psychiatry continues to prioritize therapeutic alliance and individualized patient care.