Occurrence of Blastocystis-subtypes in patients from Italy revealed association of ST3 with a healthy gut microbiota

An epidemiological survey on Blastocystis was carried out enrolling a total of 2524 subjects referred to the Umberto I Academic Hospital in Rome, for the routine parasitological exams, during 2017–2018. The studied population included a sample of immunocompromised individuals (N = 130) followed at the same hospital. DNA sequencing of the small subunit rRNA gene (SSU rDNA) locus was performed on samples positive to the coproparasitological analysis to molecular characterize the Blastocystis-subtypes. Microscopical analysis detected Blastocystis in 192/2524 (7.6%) of the enrolled subjects. It was the organism most frequently identified in the analysed faecal samples diagnosed in single infection (5.6%) or in co-infection with other enteric protozoa (2%). Furthermore, it was found mainly in immunocompromised patients (22.3%) compared to immunocompetent ones (6.8%). As expected, ST3 was the most occurring subtype identified in 40% of the subjects, followed by ST1 (29%), ST2 (16%), ST4 (12%), and ST7 (3%). Next-generation sequencing (NGS) of the 16S rDNA was performed on a sub-sample of Blastocystis-ST3-carriers, homogenous by age and gender, as well as on Blastocystis-free subjects, to profile and compare their gut bacterial composition. A higher bacterial diversity was found in ST3-Blastocystis-carriers, which exhibited a high abundance of Prevotella, Methanobrevibacter and Ruminococcus while, a high percentage of Bacteroides was found in Blastocystis-free subjects. This study evidenced the presence of Blastocystis in 7.6% of faecal samples in Italy and a high circulation of the protist among immunocompromised patients (22.3%). Molecular characterization of positive samples evidenced the occurrence of five different subtypes, including zoonotic ST such as the ST7, highlighting the risk of transmission from animals. Study of the gut microbiota composition confirms previous evidences according to which, the colonisation by Blastocystis would be linked with an eubiotic gut characterized by potentially beneficial species such as Prevotella and Ruminococcus, rather than with a dysbiotic state, with a high abundance of Enterobacteriaceae, and corroborated the role of the protist as “an old friend” of the human gut

Exploiting the indole scaffold to design compounds binding to different pharmacological targets

Several indole derivatives have been disclosed by our research groups that have been collaborating for nearly 25 years. The results of our investigations led to a variety of molecules binding selectively to different pharmacological targets, specifically the type A γ-aminobutyric acid (GABAA) chloride channel, the translocator protein (TSPO), the murine double minute 2 (MDM2) protein, the A2B adenosine receptor (A2B AR) and the Kelch-like ECH-associated protein 1 (Keap1). Herein, we describe how these works were conceived and carried out thanks to the versatility of indole nucleus to be exploited in the design and synthesis of drug-like molecules

Diruthenium(ii,iii) paddlewheel complexes: effects of bridging and axial ligands on anticancer properties

This article provides an overview of the application of diruthenium(ii,iii) paddlewheel complexes for anticancer purposes. The use of this coordinative construct is indeed attractive because it provides an excellent opportunity to combine the pharmacological properties of the dimetallic ruthenium center with those derived from the specific choice of ligands bearing a carboxylic function capable of coordination towards the Ru-Ru core. Indeed, the combination of carboxylate ligands with specific anticancer properties and the dimetallic center permits the production of new entities endowed with improved biological profiles. Additionally, these systems allow the simultaneous multiple deliveries of a drug to the target site. Nevertheless, in order to obtain the desired effects, it is mandatory to consider some relevant chemico-physical aspects such as the steric hindrance of the ligands or the possibility of their release under specific biological conditions that should be taken into account in the design of effective complexes. Accordingly, through various examples from the literature, the key features of this family of unconventional compounds are summarized here, also providing useful hints for the design of improved diruthenium(ii,iii) paddlewheel complexes

Primary hepatitis A vaccination failure is a rare although possible event: results of a retrospective study

A case of Hepatitis A occurred in a traveller in spite of a complete course of immunization with a combined HAV and HBV vaccine [Taliani G, Sbaragli S, Bartoloni A, Santini MG, Tozzi A, Paradisi F Hepatitis A vaccine failure: how to treat the threat. Vaccine 2003;21(31):4505-6]. A retrospective study was per-formed to evaluate whether the failure was primary or could be attributed to a specific lot of vaccine or to its inadequate handling and/or storage. Two distinct populations of vaccinees were selected in a 1:2 proportion. The case group (N=31) included subjects who were vaccinated in the same period and with the same lot and batch of vaccine as the case. The control group (N=62) included subjects who received different lot and batch of the same vaccine as the case group. A persisting antibody response to HAV vaccine was found among all subjects (anti-HAV > 20 mIU/ml). The overall anti-HBs seropositivity rate (anti-HBs > 10 mIU/ml) was 74%, without significant difference between the case (77%) and the control group (73%; P > 0.05). The reported Hepatitis A case can be attributed to a rare primary vaccine failure rather than to inefficacy of a specific lot of vaccine or to inappropriate vaccine handling or storage. Our study supports the indications for use of combined Hepatitis A+B immunization in travellers at risk for both infections, but stresses the need for information on correct hygienic behaviours while abroad. (c) 2006 Elsevier Ltd. All rights reserved

The added value of operator’s judgement in thyroid nodule ultrasound classification arising from histologically based comparison of different risk stratification systems.

Objective: Several ultrasound classifications for thyroid nodules were proposed but their accuracy is still debated, since mainly estimated on cytology and not on histology. The aim of this study was to test the diagnostic accuracy and the inter-classification agreement of AACE/ACE-AME, American Thyroid Association (ATA), British Thyroid Association (BTA), and Modena Ultrasound Thyroid Classification (MUT) that stratifies malignancy risk considering also the clinician subjective impression. Methods: A prospective study collecting thyroid nodule features at ultrasound and histological diagnosis was conducted. Ultrasound features were collected following a preformed checklist in candidates for surgery because of indeterminate, suspicious, or malignant cytology. All the nodules, besides the cytologically suspicious one, were blinded analyzed. MUT score was applied prospectively, and the others retrospectively. Sensitivity, specificity, diagnostic cut-off value, and accuracy of each classification were calculated. The overall agreement between classifications was tested by Bland-Altman, and agreement between single nodule analysis by different classifications by Weighted Cohen's Kappa. Results: In classifying a total of 457 nodules, MUT has the highest accuracy (AUC 0.808) and specificity (89%), followed by ATA and BTA, and finally by AACE/ACE-AME. ATA, BTA, and MUT are highly interchangeable. Considering agreement between single nodule analyses, ATA and BTA had the best (κ = 0.723); AACE/ACE-AME showed slight agreement with BTA (κ = 0.177) and MUT (κ = 0.183), and fair agreement with ATA (κ = 0.282); MUT had fair agreement with both ATA (κ = 0.291) and BTA (κ = 0.271). Conclusion: Classifications have an acceptable overall diagnostic accuracy, improved using a less rigid system that takes into consideration operator subjective impression

Risk of Seven-Day Worsening and Death: A New Clinically Derived COVID-19 Score

This monocentric, retrospective, two-stage observational study aimed to recognize the risk factors for a poor outcome in patients hospitalized with SARS-CoV-2 infection, and to develop and validate a risk score that identifies subjects at risk of worsening, death, or both. The data of patients with SARS-CoV-2 infection during the first wave of the pandemic were collected and analyzed as a derivation cohort. Variables with predictive properties were used to construct a prognostic score, which was tried out on a validation cohort enrolled during the second wave. The derivation cohort included 494 patients; the median age was 62 and the overall fatality rate was 22.3%. In a multivariable analysis, age, oxygen saturation, neutrophil-to-lymphocyte ratio, C-reactive protein and lactate dehydrogenase were independent predictors of death and composed the score. A cutoff value of 3 demonstrated a sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 93.5%, 68.5%, 47.4% and 97.2% for death, and 84.9%, 84.5%, 79.6% and 87.9% for worsening, respectively. The validation cohort included 415 subjects. The score application showed a Se, Sp, PPV and NPV of 93.4%, 61.6%, 29.5% and 98.1% for death, and 81%, 76.3%, 72.1% and 84.1% for worsening, respectively. We propose a new clinical, easy and reliable score to predict the outcome in hospitalized SARS-CoV-2 patients