In vivo activity of terpinen-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-susceptible and -resistant human pathogenic Candida species

BACKGROUND: Recent investigations on the antifungal properties of essential oil of Melaleuca alternifolia Cheel (Tea Tree Oil, TTO) have been performed with reference to the treatment of vaginal candidiasis. However, there is a lack of in vivo data supporting in vitro results, especially regarding the antifungal properties of TTO constituents. Thus, the aim of our study was to investigate the in vitro and the in vivo anti-Candida activity of two critical bioactive constituents of TTO, terpinen-4-ol and 1,8-cineole. METHODS: Oophorectomized, pseudoestrus rats under estrogen treatment were used for experimental vaginal infection with azole (fluconazole, itraconazole) -susceptible or -resistant strains of C. albicans. All these strains were preliminarily tested for in vitro susceptibility to TTO, terpinen-4-ol and 1,8-cineole for their antifungal properties, using a modification of the CLSI (formerly NCCLS) reference M27-A2 broth micro-dilution method. RESULTS: In vitro minimal inhibitory concentrations (MIC(90)) values were 0.06% (volume/volume) for terpinen-4-ol and 4% (volume/volume) for 1,8-cineole, regardless of susceptibility or resistance of the strains to fluconazole and itraconazole. Fungicidal concentrations of terpinen-4-ol were equivalent to the candidastatic activity. In the rat vaginal infection model, terpinen-4-ol was as active as TTO in accelerating clearance from the vagina of all Candida strains examined. CONCLUSION: Our data suggest that terpinen-4-ol is a likely mediator of the in vitro and in vivo activity of TTO. This is the first in vivo demonstration that terpinen-4-ol could control C. albicans vaginal infections. The purified compound holds promise for the treatment of vaginal candidiasis, and particularly the azole-resistant forms

Radiomics to predict the mortality of patients with rheumatoid arthritis-associated interstitial lung disease: A proof-of-concept study

OBJECTIVES: Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients. METHODS: High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables. RESULTS: We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36–120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56–55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05–0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06–0.82) and the flatness (HR 0.42, 95% CI 0.18–0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82–2.83) was also retained as a confounder. CONCLUSION: Radiomic analysis may predict RA-ILD patients’ mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease

Case Report A New Case of Prenatally Diagnosed Pentasomy X: Review of the Literature

Pentasomy X is a rare chromosomal abnormality probably due to a nondisjunction during the meiosis. Only four cases prenatally diagnosed were described until now. Our case is the fifth one prenatally diagnosed at 20 weeks of gestational age in a 39-yearsold woman. She underwent invasive prenatal diagnosis for her advanced maternal age without any other known risk factor. Amniocentesis performed at 17 weeks showed a female 49, XXXXX karyotype. The ultrasonographic examination revealed nonspecific signs of a mild early fetal growth retardation and no significant increased nuchal fold. The fetal autopsy and the Xray excluded major malformations. Prenatal diagnosis is often difficult due to the lack of indicative ultrasonographic findings and the rarity of described cases. The influence of the mother's age on the occurrence of penta-X syndrome has not been determined. Considering the lack of correlation between advanced maternal age and increased risk for pentasomy X, as well as the absence of typical echographic signs, evaluation of the inclusion of a noninvasive prenatal test (NIPT) that expands clinical coverage to include the X and Y chromosomes in routine prenatal diagnosis should be considered as well as three-dimensional ultrasound to detect any helpful indicative prognostic signs

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

Ariel – a window to the origin of life on early earth?

Is there life beyond Earth? An ideal research program would first ascertain how life on Earth began and then use this as a blueprint for its existence elsewhere. But the origin of life on Earth is still not understood, what then could be the way forward? Upcoming observations of terrestrial exoplanets provide a unique opportunity for answering this fundamental question through the study of other planetary systems. If we are able to see how physical and chemical environments similar to the early Earth evolve we open a window into our own Hadean eon, despite all information from this time being long lost from our planet’s geological record. A careful investigation of the chemistry expected on young exoplanets is therefore necessary, and the preparation of reference materials for spectroscopic observations is of paramount importance. In particular, the deduction of chemical markers identifying specific processes and features in exoplanetary environments, ideally “uniquely”. For instance, prebiotic feedstock molecules, in the form of aerosols and vapours, could be observed in transmission spectra in the near future whilst their surface deposits could be observed from reflectance spectra. The same detection methods also promise to identify particular intermediates of chemical and physical processes known to be prebiotically plausible. Is Ariel truly able to open a window to the past and answer questions concerning the origin of life on our planet and the universe? In this paper, we discuss aspects of prebiotic chemistry that will help in formulating future observational and data interpretation strategies for the Ariel mission. This paper is intended to open a discussion and motivate future detailed laboratory studies of prebiotic processes on young exoplanets and their chemical signatures

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution