Exosomes are a subset of extracellular vesicles (EVs) secreted by nearly all cell types and have emerged as a novel mechanism for intercellular communication within the central nervous system (CNS). These vesicles facilitate the transport of proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, playing a pivotal role in CNS development and the maintenance of homeostasis. Current evidence indicates that exosomes from CNS cells may function as either inhibitors or enhancers in the onset and progression of neurological disorders. Furthermore, exosomes have been found to transport disease-related molecules across the blood–brain barrier, enabling their detection in peripheral blood. This distinctive property positions exosomes as promising diagnostic biomarkers for neurological conditions. Additionally, a growing body of research suggests that exosomes derived from mesenchymal stem cells exhibit reparative effects in the context of neurological disorders. This review provides a concise overview of the functions of exosomes in both physiological and pathological states, with particular emphasis on their emerging roles as potential diagnostic biomarkers and therapeutic agents in the treatment of neurological diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP (p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p-value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection.

Objective: The combination and tentative correlation of a selected set of polysomnographic tests with the quantitative measurement of oxysterols of pathophysiological relevance in the cerebrospinal fluid (CSF) of patients with Alzheimer’s degenerative dementia (AD), non-Alzheimer’s degenerative dementia (NAD) and nondegenerative disorders (C) were afforded in a pilot study. Methods: Sleep efficiency, percentage of sleep time spent in nonrapid eye movement (NREM) stage 3 (N3), apnea/hypopnea index and sleep time spent with oxygen saturation <90% were recorded. Oxysterols of both enzymatic and nonenzymatic origin were quantified in the CSF of the three groups of patients by isotope-dilution gas chromatography mass spectrometry. Results: A remarkable increase in all tested oxysterols of autoxidation origin and of cholesterol was detectable in the CSF of AD and NAD patients in comparison with C patients. Of the four markers of sleep quality tested, only the percentage duration of N3 showed a net progressive reduction in NAD and AD patients. A strong inverse correlation between the CSF levels of 7k-cholesterol (7KC) and 7α-hydroxycholesterol and the duration of N3% in the recruited cohorts of patients appeared evident. Conclusions: An abnormal increase in some oxysterols of autoxidation origin, particularly of 7KC, in the CSF of patients with degenerative dementia, with the highest levels reached in AD patients, appears to be a reliable candidate biomarker of reduced duration of N3 sleep. The observed accumulation of oxysterols in the CSF seems at least in part because of impaired efficiency of the glymphatic system, which indeed reaches, under normal conditions, its maximum activity in the N3 sleep phase. A contribution of altered cholesterol metabolism to sleep quality in AD patients cannot be excluded. Significance statement: Oxysterols of nonenzymatic origin are proposed as new CSF candidate markers of sleep quality in patients with dementia.

Introduction: Several studies have previously demonstrated an increased risk of dementia and brain amyloid deposition in individuals with heterozygous NPC1 mutations. Moreover, in a recent study, we identified the first family with autosomal dominant late‐onset Alzheimer's disease (AD) caused by a heterozygous NPC1 mutation. Unfortunately, there are currently no effective treatments available for this condition. Miglustat, which impacts the metabolism of oxysterols, has been shown to exert an anti‐amyloidogenic effect in a human cellular model of AD. Methods: In our exploratory uncontrolled study, three patients from the previously published family were orally treated with miglustat for 12 months. They underwent monthly clinical evaluations and routine blood tests. Additionally, neuropsychological evaluations, brain amyloid‐PET imaging, and biochemical analyses on plasma and CSF were performed. Results: All three patients achieved clinical stability, showed a sustained reduction in serum oxysterol levels, and experienced a marked decrease in brain amyloid burden. Discussion: Based on our preliminary observations and hypothesis‐generating findings, along with the growing evidence suggesting AD as a lipid disorder, miglustat should be further tested in a larger cohort of heterozygous NPC1 mutated patients and probably evaluated as a potential disease‐modifying treatment for AD.

The assessment of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to verify the protective efficacy of available vaccines. Hospital healthcare workers play an essential role in the care and treatment of patients and were particularly at risk of contracting the SARS-CoV-2 infection during the pandemic. The vaccination protocol introduced in our hospital protected the workers and contributed to the containment of the infection’ s spread and transmission, although a reduction in vaccine efficacy against symptomatic and breakthrough infections in vaccinated individuals was observed over time. Here, we present the results of a longitudinal and prospective analysis of the anti-SARS-CoV-2 antibodies at multiple time points over a 17-month period to determine how circulating antibody levels change over time following natural infection and vaccination for SARS-CoV-2 before (T0–T4) and after the spread of the omicron variant (T5–T6), analyzing the antibody response of 232 healthy workers at the Pio XI hospital in Desio. A General Estimating Equation model indicated a significant association of the antibody response with time intervals and hospital area, independent of age and sex. Specifically, a similar pattern of antibody response was observed between the surgery and administrative departments, and a different pattern with higher peaks of average antibody response was observed in the emergency and medical departments. Furthermore, using a logistic model, we found no differences in contracting SARS-CoV-2 after the third dose based on the hospital department. Finally, analysis of antibody distribution following the spread of the omicron variant, subdividing the cohort of positive individuals into centiles, highlighted a cut-off of 550 BAU/mL and showed that subjects with antibodies below this are more susceptible to infection than those with a concentration above the established cut-off value.

Objectives: Urinary tract infections (UTIs) are very common in clinical practice. Urine culture remains the cornerstone of UTI diagnosis, but urinalysis screening for bacteriuria can improve workflow. The aim of the study was to screen for significant bacteriuria using Aution Eye AI-4510, a flow cell digital urine sediment image analyzer recently introduced in Italy. Methods: 1,096 consecutive urine samples were studied. Samples were classified into three population groups: total population (n=1,096), 0–16 years (n=79), and >65 years (n=450). Each group was subdivided into females and males. At the established cut-offs, leukocyte (WBC) count, bacterial (BACT) count, or their combination with an and/or criterion, were then used to determine positivity. Results were compared to urine culture results obtained from the same samples. Results: Best screening was found in all groups, except the pediatric one, when WBC and BACT counts were combined. The total population group performed the best: at the defined cut-offs (WBC≥177; BACT≥1,000.5), sensitivity (SE) was 90.2 %, negative predictive value (NPV) was 96.9 %. The pediatric group showed inferior screening performance: the NPV was 78.8 % and the SE was 36.4 %. In the two subgroups of >65 years, males exhibited a strong screening reliability (DOR=36.2), while females showed a poor one (DOR=11.2). Conclusions: Our findings show that the Aution Eye AI-4510 is an effective tool for screening urine samples. It quickly excludes patients who test negative for significant bacteriuria from further culturing, reducing unneeded urine cultures, and lowering expenses and workload. Furthermore, clinical decisions can be anticipated when screening is negative.