Synthesis of pyrrolo[1,2-<i>a</i>]indole-1,8(5<i>H</i>)-diones as new synthons for developing novel tricyclic compounds of pharmaceutical interest

In the course of our work aimed at developing novel heterocycles of pharmaceutical interest, a new tricycle, the tetrahydropyrrolo[1,2-a]indole-1,8-dione, has been synthesized by an intramolecular Friedel-Crafts acylation, as a synthon suitable to be functionalized to give novel compounds with potential biological properties. Also, an unusual nucleophilic α-addition to methyl propiolate by 1,5,6,7-tetrahydro-4H-indol-4-one was observed and discussed

2022: Are We Back to the pre-COVID-19 Pandemic Period in the Management of out-of-Hospital Cardiac Arrest?

Introduction: The COVID-19 pandemic caused a significant strain on the Emergency system, particularly for time-dependent diseases like Out of Hospital Cardiac Arrest (OHCA). Studies have shown an increase in the incidence of OHCA during different waves of the pandemic, but there is limited evidence on how survival rates and rescue efforts have been affected in the post-pandemic period. Methods: We performed a retrospective observational cohort study of all OHCA rescues by AREU (Agenzia Regionale Emergenza Urgenza), in the Lombardy region in March in three different years (2019, 2021 and 2022). We used rescue mission data collected in AREU’s database, where logistic information of patient rescue missions managed by the Lombardy Region’s 112 system is recorded.Results: This study was an epidemiology analysis of OHCA after the pandemic. The results showed no significant changes in the probability of receiving bystander cardiopulmonary resuscitation (22.5% vs 24.0%; p=0.41) and public access defibrillation (3.6 vs 3.2; p=0.50) compared to pre-pandemic period. However, there was a decrease in the probability of ROSC (11.5% vs 6.2%; p&lt;0.01).Conclusion: According to our analysis, there appears to be a return to the pre-pandemic phase with regard to the OHCA network. However, it remains to be pointed out that a careful study of disease networks is essential to understand the resilience of our health system and to understand whether we have returned to a system similar to the pre-pandemic phase after the COVID-19 pandemic

Epstein Barr Virus and <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> peptides are recognized in sera and cerebrospinal fluid of MS patients

Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV/MAP peptides and the IRF5/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF. An intrathecal specific synthesis of IgG against MBP and their EBV and MAP homologous as indicated by the antibody index was observed in MS patients. The humoral response against EBV, MAP, MBP and IRF5 was significantly higher in MS patients compared to OND both in serum and in CSF. The higher presence of antibodies against MBP and their MAP and EBV homologous in CSF during relapses suggests a possible role of the pathogens in enhancing inflammation

Serum BAFF levels, methypredsinolone therapy, Epstein-Barr virus and <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> infection in Multiple Sclerosis patients

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease

Type 1 Diabetes at-risk children highly recognize <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> epitopes homologous to human Znt8 and Proinsulin

Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations. Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). A higher prevalence was detected for MAP/ZnT8 pairs (62,96% T1D vs. 7,14% HCs; p &lt; 0.0001) compared to MAP/PI epitopes (22,22% T1D vs. 9,52% HCs) and decreasing trends were observed upon time-point analyses for most peptides. Similarly, classical ZnT8 Abs and GADA decreased in a time-dependent manner, whereas IAA titers increased by 12%. Responses in 0–9 year-old children were stronger than in 10–18 age group (75% vs. 69,1%; p &lt; 0.04). Younger age, female sex and concomitant autoimmune disorders contributed to a stronger seroreactivity suggesting a possible implication of MAP in multiple autoimmune syndrome. Cross-reactivity of the homologous epitopes was reflected by a high correlation coefficient (r2 &gt; 0.8) and a pairwise overlap of positivity (&gt;83% for MAP/ZnT8)

Combining HLA-DRB1-DQB1 and <i>Mycobacterium avium subspecies paratubercolosis</i> (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors?

Background: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. Methods: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. Results: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). Conclusions: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP

Studi strutturistici di isossazoli 3,5-disostituiti mediante spettroscopia ¹H-NMR

L’enzima HIV-1 integrasi rappresenta un promettente e validato target per lo sviluppo di nuovi agenti terapeutici anti-AIDS. Sono state individuate diverse classi di inibitori ed al momento i β-dichetoacidi costituiscono la più importante. Con lo scopo di progettare e sintetizzare nuovi analoghi bioisosterici, il farmacoforo costituito dalla catena β-dichetoacida è stato incorporato in un nucleo isossazolico. Sono stati quindi preparati una serie di acidi aril- ed eteroaril isossazolici ed alcuni di questi hanno mostrato attività inibitoria nei confronti dell’HIV-1 IN purificata in un range di concentrazione dell’ordine micromolare

WFD and eutrophication assessment: the role of nitrogen as a driving nutrient in shaping phytoplankton assemblages in 13 Italian water bodies

This research was carried out in the frame of the LIFE project INHABIT (Local hydro-morphology, habitat and RBMPs: new measures to improve ecological quality in South European rivers and lakes). A key action of the project was finalized to detect the relationship between nutrients on the ecological quality of water bodies and to identify management options to reduce their effects on aquatic ecosystems to be included in RBMPs, focusing, in particular, on nitrogen. The outcome of the project will serve as a basis for the implementation of Water Framework Directive river basis management plans in Italy and, possibly, in Europe. Analyses were carried out on data from 13 lakes, located in two Italian Regions, Piedmont (North-western Italy, 7 lakes; 5 natural and 2 reservoirs) and Sardinia Island (6 lakes; 1 natural, 5 reservoirs). Seasonal samples were collected in each lake, from 3 to 6, depending on environmental characteristics. The following variables were considered: water temperature, conductivity, alkalinity, pH, dissolved oxygen, SRP, TP, N-NH4, N-NO3, TN, RSi, Secchi depth and chlorophyll. Species/environment relationships were explored using multivariate statistical techniques (CCA, RDA and Generalised Additive Models). Analysis was carried out on 23 phytoplankton orders and 51 genera/species. The results pointed out an increase of cyanobacteria (Nostocales and Oscillatoriales) with the increasing nitrogen availability. Moreover, a positive response of some chlorophytes species was also observed. On the other side, diatoms declined when nitrogen concentration increased. Our findings, confirming some experimental results previously obtained, emphasize the need for a further attention towards the impact of increasing nitrogen, in particular from atmospheric inputs, when restoration plans against eutrophication are designed

In vitro bactericidal activities of various extracts of saffron (Crocus sativus L.) stigmas from Torbat-e Heydarieh, Gonabad and Khorasan, Iran

Saffron is one of the most expensive spices in the world (20,000 €/kg) and this is due not only to the high demand for its various uses such as cooking, production of staining medicines, cosmetics etc., but also for the high costs of cultivation and production. Several studies have demonstrated that differences in saffron quality are mainly due to the methodology followed in the processing of stigmas, and environmental conditions independent of the origin. Some authors found phenotypic variations within cultivated saffron, but very limited genetic diversity. The reason for the very limited genetic diversity in cultivated saffron is explained by its asexual mode of reproduction (propagation). The aim of this study was to assess the antimicrobial activity of stigma saffron, which were tested against different bacteria strains. The results obtained from the antimicrobial activity study indicate that stigmas of C. sativus have some antimicrobial effect