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Background: Molecular testing is considered the gold standard for the detection of SARS-CoV-2. This study aimed to compare the performance of the P742H SARS-CoV-2 Nucleic Acid Multiplex Detection Kit in salivary samples, with respect to the 732HF Novel Coronavirus (2019-nCoV) Nucleic Acid Detection Kit and the TaqPath COVID-19 CEIVD RT-PCR Kit, used at University-Hospital of Padova, Italy. Methods: One hundred twenty-four salivary samples selfcollected by healthcare workers (HCW) during the screening program at University-Hospital of Padova, Italy, from Oct to Nov 2022, were included in the study. RNA extraction was performed by Viral DNA and RNA Extraction Kit (Technogenetics, Lodi, Italy) and amplification by P742H and 732HF (Technogenetics, Lodi, Italy). RNA was extracted using MagNa Pure 96 DNA and Viral NA Small Volume Kit (Roche, Switzerland) for TaqPath analysis (Thermo Fisher Scientific, USA). Results: 94 samples were positive at P742H, while 30 were negative; for 732HF, 96 samples were positive, while 28 were negative, with an overall agreement of 97.5% (Cohen's = 0.930, p < 0.001). TaqPath gave 95 positive samples, and 29 negative results, with an overall agreement of 100% (Cohen's = 1.0, p < 0.001) with respect to P742H, and 97.5% (Cohen's = 0.931, p < 0.001) with respect to 732HF. Comparing cycle threshold (Ct) between the P742H and 732HF, no statistically significant differences were found (p = n.s.). Conclusion: The P742H method proved better performances than 732HF for salivary samples, both presenting the same amplification time. In addition, P742H results were comparable to those obtained through the highthroughput method TaqPath.

Objective: Salivary alpha-amylase (sAA) has been recently proposed as biomarker of stress responsiveness within the sympathetic nervous system, preferable to cortisol, since limitations related to cortisol measurement (e.g. diurnal and seasonal rhythms, drugs interferences). Several factors, as age, collection device and analytical methods, also influence sAA levels and interpretation. This study aims to assess whether sAA could be useful to evaluate the stress response, also verifying some sources of variability. Methods: To identify any sources of sAA variability, saliva samples were collected from eight healthy subjects at five different times (8:00, 10:00, 12:00, 14:00 and 16:00) over five consecutive days using two different collection devices. Saliva was then collected from 35 obstetric residents before and after a simulated shoulder dystocia scenario, one of the most traumatic birth events in the professional life of gynecologists, to assess the stress levels. Samples were analysed throughout two different assays. Heart rate (HR) of residents was also measured before and after simulation scenario. Residents self-collected two saliva samples 10 min apart on a typical day. Results: Overall, sAA levels increased significantly from morning to afternoon. Levels varied between subjects, but no differences were found between days or sampling devices. sAA activity levels in samples from 35 residents were significantly higher than those obtained before the scenario took place (about ten minutes later). These results were confirmed by two different assays. Moreover, a similar trend was observed when HR was considered. No differences were observed between samples collected 10 minutes apart on a typical day. Conclusions: Salivary alpha-amylase activity is a reliable, quick, and efficient marker for stress response, then its measurement will be of potential interest in the field of stress-related disorders. However, it is important to consider the timing of sample collection before introducing sAA in a clinical setting. [ABSTRACT FROM AUTHOR]

Ocean liming has gained attention as a potential solution to mitigate climate change by actively removing carbon dioxide (CO2) from the atmosphere. The addition of hydrated lime to oceanic surface water leads to an increase in alkalinity, which in turn promotes the uptake and sequestration of atmospheric CO2. Despite the potential of this technique, its effects on the marine ecosystem are still far from understood, and there is currently no information on the potential impacts on the concentration and quality of dissolved organic matter (DOM), which is one of the largest, most complex and yet least understood mixtures of organic molecules on Earth. The aim of this study is to provide the first experimental evidence about the potential effects of hydrated lime addition on DOM dynamics in the oceans by assessing changes in its concentration and optical properties (absorption and fluorescence). To investigate the effects of liming on DOM pools with different concentrations and quality, seawater was collected from two contrasting environments: the oligotrophic Mediterranean Sea, known for its dissolved organic carbon (DOC) concentration comparable to that observed in the oceans, and the eutrophic Baltic Sea, characterized by high DOM concentration mostly of terrestrial origin. Hydrated lime was added to both waters to reach pH values of 9 and 10. Our findings reveal that the addition of hydrated lime has a noticeable effect on DOM dynamics in both the Mediterranean Sea and Baltic Sea, determining a reduction in DOC concentration and a change in the optical properties (absorption and fluorescence) of DOM. These effects, detectable at pH 9, become significant at pH 10 and are more pronounced in the Mediterranean Sea than in the Baltic Sea. These potential short-term effects should be considered within the context of the physicochemical properties of seawater and the seasonal variability. [ABSTRACT FROM AUTHOR]

A submerged elevation located off the coast of Le Castella, a small village on the Ionian Coast of Calabria (Italy) populated for thousands of years that features notable archaeological remains from the Great Greece (Magna Graecia) and the Middle Ages, was investigated through in-depth, multidisciplinary, geoarchaeological research. This submarine elevation, once aligned with the marine terrace MIS 3 of Le Castella and still completely emerged between 10 and 8 ka years ago, slowly sank due to erosion and local tectonic-structural subsidence and was also favoured by a submerged normal fault that cuts the terrace in two. The dismantling and sinking of this part of the marine terrace has significantly changed the Late Holocene shorelines, with notable consequences on a topographic and archaeological level. In fact, one of the consequences of the sinking of this ancient promontory was the disappearance of two small islands that were reported to be right in front of Le Castella by numerous historical and cartographic sources. In the last decades, there has been a scientific debate over the existence of these islets, but no convincing evidence has been found about their actual presence up until now. This research, funded by the Marine Protected Area "Capo Rizzuto", was conducted by means of underwater archaeological and geological surveys, geophysical seabed mapping systems, and both direct and instrumental optical surveys made with an Autonomous Surface Vehicle. The outcomes allow us to confirm the presence of these two partially emerged rock bodies up to half a millennium ago. In addition, the presence of anthropogenic extrabasinal materials in a marine area corresponding to one of the highest points of the submerged elevation allows us to define the exact position of one of the two islets. These archaeological findings have been subject, for the first time ever, to a thorough topographical and architectural analysis, then compared with other near and very similar submerged structures. On the basis of these comparisons, the findings should be attributed to the Byzantine Age or, at most, to the Middle Ages. In-depth archival research on portolan charts and navigation maps, in many cases unpublished and dating from the Middle Ages to the early 18th century, supports the results of our marine investigations from a historical point of view. [ABSTRACT FROM AUTHOR]

The lower Messinian Calcare di Rosignano Formation (Tuscany, Italy, 43° N) preserves one of the youngest and northernmost examples of coral reefs in the Mediterranean. The outcropping succession of the Acquabona quarry consists of four main facies, namely, in ascending stratigraphic order: (1) coral boundstone, (2) coralline algal rudstone, (3) serpulid floatstone to packstone, and (4) peloidal packstone to grainstone. The succession displays a trend toward increasingly more shallow conditions and progressively more restricted water circulation. The coral reef displays a limited coral biodiversity and a remarkable abundance of heterotrophs, similar to modern coral reefs developed at the edges of the ecological niche of symbiont-bearing colonial corals. The widespread presence of coral colonies pervasively encrusted by coralline algae and benthic foraminifera suggests that short-term environmental perturbations caused temporary shutdowns of the coral-dominated carbonate factory. Moving upwards, there are fewer corals and more highly adaptable carbonate producers like coralline algae and serpulids. This suggests that the decline of corals had been caused by the conditions in the basin becoming more stressful, up to the collapse of the coral community. The overall succession indicates that coral-dominated ecosystems located at the edges of the coral zone are very sensitive; they can be affected even by minor perturbations and easily collapse if negative conditions persist. [ABSTRACT FROM AUTHOR]

Sepsis is a complex disorder caused by a dysregulated host response to infection, with high levels of morbidity and mortality. Treatment aimed to modulate immune response and maintain vascular function is still one of the major clinical challenges. This study was designed to test the effect of the small molecule 1-Piperidine Propionic Acid (1-PPA) as molecular targeted agent to block protease-activated receptor 2 (PAR2), one of the major modulators of inflammatory response in LPS-induced experimental endotoxemia. In the THP-1 cell line, LPS-induced cytokine expression was inhibited by 1-PPA in a dose-dependent manner. In LPS-injected mice, treatment with 1-PPA was effective in reducing mortality and sepsis-related symptoms and improved cardiac function parameters. After 6 h from LPS injection, a significant decrease in IL-6, IL-1β, and IL-10 was observed in the lung tissue of 1-PPA-treated mice, compared to controls. In these mice, a significant decrease in vasoactive molecules, especially kininogen-1, was also observed, mainly in the liver. Histopathological analysis confirmed typical features of sepsis in different organs and these findings were markedly reduced in mice treated with 1-PPA. These data demonstrate the effectiveness of 1-PPA in protecting the whole organism from sepsis-induced damage. [ABSTRACT FROM AUTHOR]

Context The clinical presentation of Cushing syndrome (CS) overlaps with common conditions. Recommended screening tests are serum cortisol after 1-mg overnight dexamethasone suppression test (DST), urinary free cortisol (UFC), and late-night salivary cortisol (LNSC). Objective We analyzed the diagnostic accuracy of screening tests in 615 patients without CS (263 suspected CS, 319 adrenal and 33 pituitary incidentaloma) and 40 with CS. Methods Principal component analysis, K-means clustering, and neural network were used to compute an integrated analysis among tests, comorbidities, and signs/symptoms of hypercortisolism. Results The diagnostic accuracy of screening tests for CS was high; DST and UFC were slightly superior to LNSC. The threshold of DST should be adapted to the population considered, especially in adrenal incidentaloma (AI) with mild autonomous cortisol secretion: The cutoff to differentiate CS should be increased to 196 nmol/L. Diabetes, hypertension, and obesity were more common in patients without CS: The direction of their vectors was not aligned and their correlation with screening tests was poor. Clustering allowed us to differentiate those patients without CS into cluster 1 (aged osteoporotic patients with impaired screening tests), cluster 2 (hypertensive and metabolic phenotype), and cluster 3 (young individuals with a low likelihood of overt CS). A neural network model that combined screening tests and clinical presentation was able to predict the CS diagnosis in the validation cohort with 99% precision and 86% accuracy. Conclusion Despite the high diagnostic accuracy of screening tests to detect CS, cortisol-related comorbidities or AI should be considered when interpreting a positive test. [ABSTRACT FROM AUTHOR]

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single‐nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV‐SNPs and 133,615 CoRSIV‐mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10−5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan‐meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association. [ABSTRACT FROM AUTHOR]

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies. [ABSTRACT FROM AUTHOR]