41 research outputs found
Kinetics of dried blood spot-measured anti-SARS-CoV2 Spike IgG in mRNA-vaccinated healthcare workers
Introduction: One of the major criticisms facing the research community during SARS-CoV2 pandemic was the lack of large-scale, longitudinal data on the efficacy of the SARS-CoV2 mRNA vaccines. Currently, even if COVID-19 antiviral treatments have been authorized by European Medicine Agency, prevention through approved specific vaccines is the best approach available in order to contain the ongoing pandemic. Objectives: Here, we studied the antibody kinetic over a one-year period from vaccination with the Pfizer-BioNTech (Pfizer) vaccines and subsequent boosting with either the BioNTech or Moderna (Spikevax) vaccines in a large cohort of 8,071 healthcare workers (HCW). We also described the impact of SARS-CoV2 infection on antibody kinetic over the same period. Methods: We assessed the anti SARS-CoV2 Spike IgG antibody kinetic by the high throughput dried blood spot (DBS) collection method and the GSP®/DELFIA® Anti-SARS-CoV2 IgG assay (PerkinElmer®). Results: Our data support existing models showing that SARS-CoV2 vaccination elicits strong initial antibodies responses that decline with time but are transitorily increased by administering a vaccine booster. We also showed that using heterologous vaccine/booster combinations a stronger antibody response was elicited than utilizing a booster from the same vaccine manufacturer. Furthermore, by considering the impact of SARS-CoV2 infection occurrence in proximity to the scheduled booster administration, we confirmed that booster dose did not contribute significantly to elicit higher antibody responses. Conclusion: DBS sampling in our large population of HCWs was fundamental to collect a large number of specimens and to clarify the effective mRNA vaccine-induced antibody kinetic and the role of both heterologous boosters and SARS-CoV2 infection in modulating antibody responses
Extracellular vesicles from adipose mesenchymal stem cells target inflamed lymph nodes in experimental autoimmune encephalomyelitis
Background aims: Adipose mesenchymal stem cells (ASCs) represent a promising therapeutic approach in inflammatory neurological disorders, including multiple sclerosis (MS). Recent lines of evidence indicate that most biological activities of ASCs are mediated by the delivery of soluble factors enclosed in extracellular vesicles (EVs). Indeed, we have previously demonstrated that small EVs derived from ASCs (ASC-EVs) ameliorate experimental autoimmune encephalomyelitis (EAE), a murine model of MS. The precise mechanisms and molecular/cellular target of EVs during EAE are still unknown. Methods: To investigate the homing of ASC-EVs, we intravenously injected small EVs loaded with ultra-small superparamagnetic iron oxide nanoparticles (USPIO) at disease onset in EAE-induced C57Bl/6J mice. Histochemical analysis and transmission electron microscopy were carried out 48 h after EV treatment. Moreover, to assess the cellular target of EVs, flow cytometry on cells extracted ex vivo from EAE mouse lymph nodes was performed. Results: Histochemical and ultrastructural analysis showed the presence of labeled EVs in lymph nodes but not in lungs and spinal cord of EAE injected mice. Moreover, we identified the cellular target of EVs in EAE lymph nodes by flow cytometry: ASC-EVs were preferentially located in macrophages, with a consistent amount also noted in dendritic cells and CD4+ T lymphocytes. Conclusions: This represents the first direct evidence of the privileged localization of ASC-EVs in draining lymph nodes of EAE after systemic injection. These data provide prominent information on the distribution, uptake and retention of ASC-EVs, which may help in the development of EV-based therapy in MS
Adherence to Herpes Zoster (Shingles) Catch-Up Campaign at the Romagna Local Health Authority (Italy), a Multi-Center Retrospective Observational Study
: Herpes Zoster (shingles) is an infection that occurs when varicella-zoster virus reactivates from the latent state. Incidence and severity of Herpes Zoster disease increase with age. Antiviral drugs are the elective treatment; however, prevention of disease reactivation through effective and safe vaccines is available in Italy out-of-pocket from age 65 onwards. The Romagna Local Health Authority (northern Italy) administered catch-up vaccinations in March-May 2022 for immunizations not performed during the COVID-19 pandemic. In this study, adherence rates to the catch-up campaign and recall activities adopted in two centers were investigated. The uptakes for only the catch-up vaccinations were 11.4% and 12.4%. Having suffered from Herpes Zoster or having family members who suffered from it would not seem to be drivers of increased uptake. Although sending text-messages to all involved patients was the main motivation for vaccine uptake (85.7-95.1%), word of mouth and web/news advertising also contributed to adoption in Center No. 2. In both centers, the need for greater synergy between public health departments and general practitioners to engage their patients emerged, as did the need for additional recall measures. Studying the main drivers of vaccine hesitancy, especially at the local level, can help in targeting campaigns and catch-up activities in order to achieve widespread acceptance
New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics
Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut-brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance. Recent advances proposed epigenetic factors as possible regulators of several mechanisms involved in IBS pathophysiology. These epigenetic factors include biomolecular mechanisms inducing chromosome-related and heritable changes in gene expression regardless of DNA coding sequence. Accordingly, altered gut microbiota may increase the production of metabolites such as sodium butyrate, a prominent inhibitor of histone deacetylases. Patients with IBS showed an increased amount of butyrate-producing microbial phila as well as an altered profile of methylated genes and micro-RNAs (miRNAs). Importantly, gene acetylation as well as specific miRNA profiles are involved in different IBS mechanisms and may be applied for future diagnostic purposes, especially to detect increased gut permeability and visceromotor dysfunctions. In this review, we summarize current knowledge of the role of epigenetics in IBS pathophysiology
Vitamin C Deficiency in Patients With Acute Myeloid Leukemia
Vitamin C has been shown to play a significant role in suppressing progression of leukemia through epigenetic mechanisms. We aimed to study the role of vitamin C in acute myeloid leukemia (AML) biology and clinical course. To this purpose, the plasma levels of vitamin C at diagnosis in 62 patients with AML (including 5 cases with acute promyelocytic leukemia, APL),7 with myelodysplastic syndrome (MDS), and in 15 healthy donors (HDs) were studied. As controls, vitamins A and E levels were analysed. Expression of the main vitamin C transporters and of the TET2 enzyme were investigated by a specific RQ-PCR while cytoplasmic vitamin C concentration and its uptake were studied in mononuclear cells (MNCs), lymphocytes and blast cells purified from AML samples, and MNCs isolated from HDs. There were no significant differences in vitamin A and E serum levels between patients and HDs. Conversely, vitamin C concentration was significantly lower in AML as compared to HDs (p<0.0001), inversely correlated with peripheral blast-counts (p=0.029), significantly increased at the time of complete remission (CR) (p=0.04) and further decreased in resistant disease (p=0.002). Expression of the main vitamin C transporters SLC23A2, SLC2A1 and SLC2A3 was also significantly reduced in AML compared to HDs. In this line, cytoplasmic vitamin C levels were also significantly lower in AML-MNCs versus HDs, and in sorted blasts compared to normal lymphocytes in individual patients. No association was found between vitamin C plasma levels and the mutation profile of AML patients, as well as when considering cytogenetics or 2017 ELN risk stratification groups. Finally, vitamin C levels did not play a predictive role for overall or relapse-free survival. In conclusion, our study shows that vitamin C levels are significantly decreased in patients with AML at the time of initial diagnosis, further decrease during disease progression and return to normal upon achievement of CR. Correspondingly, low intracellular levels may mirror increased vitamin C metabolic consumption in proliferating AML cells
Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia
The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative
26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017
This work was produced as part of the activities of FAPESP Research,\ud
Disseminations and Innovation Center for Neuromathematics (grant\ud
2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud
FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud
supported by a CNPq fellowship (grant 306251/2014-0)
Spermatogenesis, epididymis morphology and plasma sex steroid secretion in the male lizard Podarcis sicula exposed to diuron.
The present study investigates the effects of diuron, a substituted urea-based herbicide, in the male lizard Podarcis sicula utilizing quantitative and qualitative morphological features of the reproductive system and endocrinological analysis. Besides the control group, lizards were divided into three groups ([a], [b], [c]) (n = 6/group) and put for 3 weeks in terraria on polluted soil substrate sprayed with 3.75 L/ha of herbicide Toterbane 50F (50% diuron). Each terrarium was supplemented either with drinking water contaminated by herbicide (i.e. 1.08 g/ml of diuron; group [a]), or with food contaminated by herbicide (i.e. 5.4 mg of diuron; group [b]), or with drinking water and food contaminated as described above (group [c]).
None of the animals exposed to the contaminant showed any signs of general toxicity or death during the course of the experiments. Severe testicular effects are evidenced in all herbicide-treated groups, although, such effects are of a greater magnitude in lizards exposed to contaminated water (groups [a] and [c]). The main degenerative changes observed include: 1) a significant decrease in the mean gonadosomatic index of 55% in group [a] (P<0.001), 21% in group [b] (P<0.01) and 34% in group [c] (P<0.001) compared with control group; 2) a significant shrinking (P<0.001) of seminiferous tubule diameter (more than 60% of the control) in groups [a] and [c], and about of 18% in group [b] (P<0.01); 3) a significant decrease in the crude numbers of spermatogonia of 92% in group [a] (P<0.001), 27% in group [b] (P<0.01) and 62% in group [c] (P<0.001) compared with control group. A complete loss of meiotic and mature germ cells in groups [a] and [c], and a reduction of primary spermatocytes, secondary spermatocytes and spermatids (more than 27% of the control) and a decrease of spermatozoa (more than 90% of the control) in group [b]; 4) an hypertrophy of interstitial connective tissue which contains numerous lymphocytes, neutrophils and monocytes.
The decrease and/or loss of germ cells seems to be related to an induction of inflammation (necrosis) rather than to apoptotic processes. Indeed, this hypothesis is supported by TUNEL-assay which failed to reveal any apoptotic cells either in the seminiferous epithelium or in the interstitial space in the testis of all exposed groups.
Also the epididymis appears affected by diuron exposure. In particular, in experimental groups [a] and [c] it is regressed with abundant connective tissue and low epithelial cells without secretory granules, whereas in group [b] it appears partially regressed, with some secretory granules still present.
At the same time, an impairment of the plasma sex hormone levels is observed in treated lizards, as evidenced by RIA analysis. Testosterone values significantly decrease of 43% in group [a] (P<0.001), 34% in group [b] (P<0.01) and 52% in group [c] compared with control group. Instead, 17-estradiol plasma content is undetectable in all diuron-exposed lizards.
Taken together, the results presented here indicate that diuron exposure resulted in direct male reproductive toxicity and reveal that this lizard is suitable as a laboratory reptile species for toxicological investigations