Radon concentration in self-bottled mineral spring waters as a possible public health issue

Since 2013, the Council Directive 2013/51/Euratom has been regulating the content of radioactive substances in water intended for human consumption. However, mineral waters are exempted from this regulation, including self-bottled springs waters, where higher radon concentration are expected. Therefore, a systematic survey has been conducted on all the 33 mineral spring waters of Lazio (a region of Central Italy) in order to assess if such waters, when self-bottled, may be of concern for public health. Waters have been sampled in two different ways to evaluate the impact of bottling on radon concentration. Water sampling was possible for 20 different spring waters, with 6 samples for each one. The results show that 2 (10%) of measured mineral spring waters returned radon concentrations higher than 100 Bq L−1, i.e., the parametric value established by the Council Directive. These results, if confirmed by other surveys involving a higher number of mineral spring waters, would suggest regulating also these waters, especially in countries like Italy for which: (i) mineral water consumption is significant; (ii) mineral concession owners generally allow the consumers to fill bottles and containers, intended for transport and subsequent consumption, directly from public fountains or from fountains within the plant; (iii) the consumers’ habit of drinking self-bottled mineral water is widespread

Two cases of asbestosis and one case of rounded atelectasis due to non-occupational asbestos exposure

Asbestos is a well-known cause of several neoplastic (malignant mesothelioma, lung cancer) and non-neoplastic (asbestosis, pleuropathies) occupational diseases. Lower-level exposure in the general environment may induce pleural plaques and thickenings, and is associated with an increased mesothelioma risk. We present two patients (a 68-year-old man and a 72-year-old woman) who developed asbestosis (in association with pleural plaques and calcifications), and a 78-year-old man who developed rounded atelectasis (with pleural plaques and benign effusion), after living for several decades in the proximity of large Italian asbestos-cement plant. None of them had been exposed to asbestos occupationally. Besides living in a contaminated area, the woman used to clean the work clothes of her brother, who was employed in the local asbestos factory. The three cases indicate that non-neoplastic, long-latency asbestos-related diseases which are usually observed as a consequence of occupational exposures, may rarely develop in subjects living in contaminated geographical sites and buildings. These unusual environmental diseases raise the diagnostic problem of differentiating them from other, more common respiratory illnesses, and impose the duties of patient notification, assessment and follow-up, to assess the possibility of progression of disease and increased neoplastic risk

Toward multitasking pharmacological COX-targeting agents: Non-steroidal anti-inflammatory prodrugs with antiproliferative effects

The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2, 3-dihydro-1H-cyclopenta[b]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out. Cytotoxicity, cytofluorimetry, and protein expression assays on prodrugs were also performed to assess their potential as antiproliferative agents that could help hypothesize an effective use as anticancer therapeutics. Encouraging results suggest that the studied compounds could act not only as precursors of the anti-inflammatory metabolite, but also as direct antiproliferative agents. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention

Experimental data based machine learning classification models with predictive ability to select in vitro active antiviral and non-toxic essential oils

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor studies involved essential oil inspection as potential anticancer and antiviral natural remedies. In line with the authors previous reports the investigation of an in-house library of extracted essential oils as a potential blocker of HSV-1 infection is reported herein. A subset of essential oils was experimentally tested in an in vitro model of HSV-1 infection and the determined IC50s and CC50s values were used in conjunction with the results obtained by gas-chromatography/mass spectrometry chemical analysis to derive machine learning based classification models trained with the partial least square discriminant analysis algorithm. The internally validated models were thus applied on untested essential oils to assess their effective predictive ability in selecting both active and low toxic samples. Five essential oils were selected among a list of 52 and readily assayed for IC50 and CC50 determination. Interestingly, four out of the five selected samples, compared with the potencies of the training set, returned to be highly active and endowed with low toxicity. In particular, sample CJM1 from Calaminta nepeta was the most potent tested essential oil with the highest selectivity index (IC50 = 0.063 mg/mL, SI > 47.5). In conclusion, it was herein demonstrated how multidisciplinary applications involving machine learning could represent a valuable tool in predicting the bioactivity of complex mixtures and in the near future to enable the design of blended essential oil possibly endowed with higher potency and lower toxicity

Stabilnost amlodipin besilata i atenolola u jednoslojnim i dvoslojnim tabletama

Multi-drug tablets of amlodipine besylate and atenolol were prepared as either mono-layer (mixed matrix) or bi-layer tablets containing each drug in a separate layer by using similar excipients and processing. Each tablet batch was packed in strip and blister packs and kept under accelerated temperature and humidity conditions. The stability of two tablet and packaging types was compared by HPLC analysis after 0, 1, 3 and 4.5 months and expressed as the content of intact amlodipine and atenolol. The content of atenolol did not decline regardless of tablet and packaging type. Amlodipine content in bi-layer tablets decreased to about 95 and 88% when packed in strips and blisters, respectively. When prepared as mono-layer tablets, the content decreased to 72 and 32%, respectively. The study revealed that the bi-layer tablet formulation was more stable than the mono-layer type. Further, the stability was increased when the tablets were packed in aluminium strips as compared to PVC blisters.Tablete s amlodipinom i atenololom pripremljene su ili u obliku jednoslojne tablete (miješani matriks) ili kao dvoslojne tablete (lijekovi u zasebnim slojevima) koristeći slične pomoćne tvari i uvjete tabletiranja. Tablete su pakirane u dvije vrste pakiranja, aluminijske folije (strip) ili PVC (blister) i čuvane u uvjetima ubrzanog starenja. Stabilnost je određivana pomoću HPLC metode nakon 0, 1, 2, 3 i 4,5 mjeseci i izražena kao sadržaj intaktnog lijeka. Sadržaj atenolola nije se značajno promijenio bez obzira na tip tablete ili pakiranje. Sadržaj amlodipina u dvoslojnim tabletama smanjio se na 95 % (tablete u strip pakiranju) i 88 % (tablete u blister pakiranju). Istodobno, u jednoslojnom tipu kombiniranih tableta sadržaj se smanjio na 72 % (strip pakiranje) i 32 % (blister pakiranje). Rezultati pokazuju da su dvoslojne tablete s amlodipinom i atenololom stabilnije od jednoslojnih. Štoviše, pakiranje tableta u aluminijsku foliju u obliku strip pakiranja povećava njihovu stabilnost u usporedbi s PVC pakirnim materijalom (blister)

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

Resting metabolic rate and respiratory quotient in human longevity

Significant changes in body composition, body fat distribution, and resting metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity pointed out that long-lived subjects are less prone to the anthropometrics and metabolic derangement normally observed in the elderly. Indeed, the relationship between energy expenditure and longevity has been poorly investigated. Thus, energy expenditure parameters of 28 long-lived subjects were assessed and compared with those of 26 adults and 27 younger elderly. All subjects enrolled were female. In the whole population, RMR was negatively correlated with age (P < 0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but not body mass index as significant and independent determinants. Splitting the whole study group into subgroups according to age, long-lived subjects had oxygen volume, carbon dioxide volume, and Rq significantly higher than aged subjects but lower than adult subjects. In addition, long-lived subjects had total volume of expired air and RMR greater than aged subjects but not different from ones found in adults. In long-lived subjects, Rq was negatively correlated with percent body fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No significant associations of RMR and Rq with FFM were found. In conclusion, our data demonstrate that human longevity seems protected toward an age-related decline. It is likely that the lack of the anthropometrics derangement may preserve long-lived subjects from the age-related decrease in energy metabolism

Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans

Background: The cline of human genetic diversity observable across Europe is recapitulated at a micro-geographic scale by variation within the Italian population. Besides resulting from extensive gene flow, this might be ascribable also to local adaptations to diverse ecological contexts evolved by people who anciently spread along the Italian Peninsula. Dissecting the evolutionary history of the ancestors of present-day Italians may thus improve the understanding of demographic and biological processes that contributed to shape the gene pool of European populations. However, previous SNP array-based studies failed to investigate the full spectrum of Italian variation, generally neglecting low-frequency genetic variants and examining a limited set of small effect size alleles, which may represent important determinants of population structure and complex adaptive traits. To overcome these issues, we analyzed 38 high-coverage whole-genome sequences representative of population clusters at the opposite ends of the cline of Italian variation, along with a large panel of modern and ancient Euro-Mediterranean genomes. Results: We provided evidence for the early divergence of Italian groups dating back to the Late Glacial and for Neolithic and distinct Bronze Age migrations having further differentiated their gene pools. We inferred adaptive evolution at insulin-related loci in people from Italian regions with a temperate climate, while possible adaptations to pathogens and ultraviolet radiation were observed in Mediterranean Italians. Some of these adaptive events may also have secondarily modulated population disease or longevity predisposition. Conclusions: We disentangled the contribution of multiple migratory and adaptive events in shaping the heterogeneous Italian genomic background, which exemplify population dynamics and gene-environment interactions that played significant roles also in the formation of the Continental and Southern European genomic landscapes

Upper limb amputees can be induced to experience a rubber hand as their own

We describe how upper limb amputees can be made to experience a rubber hand as part of their own body. This was accomplished by applying synchronous touches to the stump, which was out of view, and to the index finger of a rubber hand, placed in full view (26 cm medial to the stump). This elicited an illusion of sensing touch on the artificial hand, rather than on the stump and a feeling of ownership of the rubber hand developed. This effect was supported by quantitative subjective reports in the form of questionnaires, behavioural data in the form of misreaching in a pointing task when asked to localize the position of the touch, and physiological evidence obtained by skin conductance responses when threatening the hand prosthesis. Our findings outline a simple method for transferring tactile sensations from the stump to a prosthetic limb by tricking the brain, thereby making an important contribution to the field of neuroprosthetics where a major goal is to develop artificial limbs that feel like a real parts of the body