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The 30–150 m bathymetric range is commonly adopted in the literature to constrain the mesophotic zone. However, such depth interval varies depending on sunlight penetration, which is primarily a function of solar radiation incidence and water clarity. This is especially obvious in the Mediterranean Sea with its peculiar biophysical properties. Integrating information on light regime in the estimation of the bathymetric range of the mesophotic zone would provide a more robust definition, orienting conservation actions targeting its ecosystems. We present a first assessment of the spatial and vertical extension of the mesophotic zone in the Mediterranean Sea based upon light penetration, comparing our prediction with literature data. Our study also represents a baseline to monitor future variations in the bathymetric interval associated with the mesophotic zone in the Mediterranean Sea in relation to global changes.

Several molecules present in the diet, including flavonoids, can inhibit the growth of cancer cells with an ability to act as “chemopreventers”. Their cancer-preventive effects have been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. The antioxidant activity of chemopreventers has recently received a great interest, essentially because oxidative stress participates in the initiation and progression of different pathological conditions, including cancer. Since antioxidants are capable of preventing oxidative damage, the wide use of natural food-derived antioxidants is receiving greater attention as potential anti-carcinogens. Among flavonoids, quercetin (Qu) is considered an excellent free-radical scavenging antioxidant, even if such an activity strongly depends on the intracellular availability of reduced glutathione. Apart from antioxidant activity, Qu also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells. In this review we discuss the molecular mechanisms that are based on the biological effects of Qu, and their relevance for human health.

The Gulf of Aqaba transform plate boundary is a source of destructive teleseismic earthquakes. Seismicity is concentrated in the central sub-basin and decreases to both the north and south. Although principally a strike-slip plate boundary, the faulted margins of the Gulf display largely dip-slip extensional movement and accompanying footwall uplift. We have constrained rates of this uplift by measurements of elevated Pleistocene coral terraces. In particular the terrace that formed during the last interglacial (~125 ka) is found discontinuously along the length of the Gulf at elevations of 3 to 26 m. Global sea level was ~7 m higher than today at 125 ka indicating net maximum tectonic uplift of ~19 m with an average rate of ~0.015 cm/yr. Uplift has been greatest adjacent to the central sub-basin and like the seismicity decreases to the north and south. We suggest that the present pattern of a seismically active central region linked to more aseismic areas in the north and south has therefore persisted for at least the past 125 kyr. Consequently the potential for future destructive earthquakes in the central Gulf is greater than in the sub-basins to the north and south.

BackgroundMacrophages strongly contribute to the pathogenesis of rheumatoid arthritis (RA), initiating the inflammatory response, the join damage, but also may promote the resolution of inflammation and the restoration of tissue immune-homeostasis [1,2]. This seems to be related to an unbalanced immunological response mediated by macrophages through their polarization into “classically” and “alternatively” activated phenotypes (M1 or M2) [3,4]. However, little is known about the M1 and M2 phenotype of their circulating precursors (monocytes) in the peripheral blood (PB) and the synovial fluid (SF) of RA patients.ObjectivesTo characterise the polarization status (M1 and M2) of PB and SF monocytes of RA patients together with their distribution in the monocyte subsets by flow cytometry (FC).MethodsNineteen RA patients not yet treated with biological DMARDs (mean age 62±14 years), who fulfilled the 2010 ACR/EULAR classification criteria for RA and treated in accordance with EULAR recommendation, as well as 19 age-matched healthy subjects (HSs) were enrolled after signed informed consent. PB and SF cells were collected from each RA patient, whereas only PB cells were collected from HSs.The expression of CD14 and CD16 surface markers allowed to identify the monocyte population and the monocyte subsets: “classical”(CD14++CD16-), “intermediate”(CD14++CD16+), and “non-classical”(CD14-CD16+).The M1 phenotype (M1 monocytes) was identified by the evaluation of CD80, CD86, TLR2 and TLR4, whereas the M2 phenotype (M2 monocytes) was identified evaluating CD204, CD163 and CD206 surface markers.Results were expressed as percentage of positive cells over total leukocytes from PB and SF. Statistical analysis was carried out by Mann-Whitney non-parametric test.ResultsIn RA patients, the percentage of CD14++CD16+monocytes was significantly higher in PB compared to that in HS (p<0.001), and it was higher in SF compared to PB (p<0.05). The percentage of CD14-CD16+monocytes was significantly increased in RA-PB compared to HS-PB and RA-SF (p<0.01; p<0.05).RA patients were characterized by an increased percentage of M1 monocytes (CD80+CD86+TLR2+TLR4+CD204-CD163-CD206-cells) in PB compared to HSs and compared to RA-SF.The percentage of M2 monocytes (CD204+CD163+CD206+CD80-CD86-TLR2-TLR4-cells) was also increased in RA-PB compared to HS-PB and to RA-SF, but this increase was lower and not significant than that observed for M1 monocytes. Moreover, the M1-M2 monocyte ratio was 8:1in RA-PB.Therefore, in RA patients, circulating M1 monocytes belonged to the “non-classical” subset, whereas M2 monocytes belonged to the “classical” subset.The percentage of circulating mixed M1/M2 monocytes (CD80+CD86+TLR2+TLR4+CD204+CD163+CD206+cells) was higher in RA patients compared to HSs. Moreover, in RA patients, the percentage of these cells was higher in SF than in PB and they primarily belonged to the “intermediate” monocyte subset. Interestingly, the highest percentage of M2 and mixed M1/M2 monocytes was observed in PB and SF of RA patients receiving a higher daily (25mg) and cumulative glucocorticoid dosages.ConclusionThe results confirm that RA is an immune-inflammatory disease mainly mediated by both M1 monocytes and macrophages, as demonstrated by the increase in the percentage of circulating M1 monocytes. Glucocorticoids might contribute to the M1 to M2 transition, which characterizes RA patients under remission by increasing mixed M1/M2 and M2 monocyte percentage.References[1]Okabe Y et al. Nat Immunol. 2016;17:9–17.[2]Kurowska-Stolarska M, et al. Nat Rev Rheumatol. 2022;18:384-97.[3]Cutolo M, et al. Front Immunol. 2022;13:867260.[4]Ross EA, et al. Front Immunol. 2021;12:708186.Acknowledgements:NIL.Disclosure of InterestsStefano Soldano: None declared, Emanuele Gotelli: None declared, Paola Montagna: None declared, Rosanna Campitiello: None declared, Alberto Sulli: None declared, Vanessa Smith: None declared, Maurizio Cutolo Grant/research support from: BMS, Boehringer, Amgen.

Among the cells involved in the inflammatory process of rheumatoid arthritis (RA) [1], macrophages play a key role through their capacity to polarize into “classically” or “alternatively” activated phenotypes (M1 or M2) and making macrophages important players for the inflammatory cascade or for the anti-inflammatory reaction, respectively [2]. CTLA4-Ig fusion protein (abatacept) has been shown to contribute to macrophage shift from M1 to M2 [3]. We aimed to investigate the effects of abatacept to induce the polarization from the pro-inflammatory M1 phenotype into the anti-inflammatory M2 phenotype in cultured human macrophages obtained from RA patients' and healthy subjects'(HS) circulating monocytes. Cultured monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of three early RA patients and ten HS, after signing informed consent and Ethics Committee approval. Cells were treated with phorbol myristate acetate (PMA) [5ng/ml] for 24 hours (hrs) to induce their differentiation into monocyte-derived macrophages (MDMs). Therefore, cultured HS MDMs were stimulated with lipopolysaccharides [LPS, 1mg/mL] for 4hrs [4] in order to induce their polarization into a pro-inflammatory M1 phenotype and then treated or not with abatacept at the concentrations of 100mg/mL and 500mg/mL for 3, 12, 24 and 48hrs. Cultured RA MDMs, were directly treated with abatacept as previous described. Cultured HS and RA MDMs without any pro-inflammatory stimuli and abatacept treatment were used as respective control. The transition of MDMs from M1 to M2 phenotype was evaluated through gene expression and protein synthesis of M2 macrophage markers, namely scavenger receptors (CD163 and CD204), and mannose receptor-1 (CD206) by quantitative real-time polymerase chain reaction (PCR) and by Western blotting. The statistical analysis evaluation was carried out by GraphPad Prism 8 analysis software using the Wilcoxon non-parametric t-test. Any p-value lower than 0.05 was considered as statistically significant. Results were indicated as median±standard deviation (SD). In cultured RA MDMs (three cases), abatacept upregulated the gene expression of all investigated M2 markers, specifically after 12hrs of treatment with the concentration of 100mg/mL. In these cells, abatacept upregulated only the CD204 protein synthesis with more evidence at 24hrs of treatment and with the 500mg/mL concentration. In cultured HS MDMs (ten cases), abatacept upregulated the gene expression of M2 markers, significantly for that of CD206 [at 3hrs with 100mg/mL concentration, p= 0.0312] and CD163 [at 12hrs with 500mg/mL concentration, p= 0.0312]. Moreover, in these cells, abatacept significantly upregulated the protein synthesis of CD206 [at 48hrs with 500mg/mL concentration, p= 0.0195] and CD204 [at 24hrs with 100mg/mL concentration, p= 0.0156; both at 24 and 48hrs with 500mg/mL concentration, p= 0.0234]. Preliminary data seem to indicate that abatacept can promote the in vitro shift from the M1 into the M2 macrophage phenotype, by upregulating specific markers (CD163, CD204, CD206) in cultured M1-MDMs from RA patients and in M1 macrophages induced from HS. [1]McInnes IB, et al. N Engl J Med 2011;365:2205–19. [2]Fujii M, et al. Biochem Biophys Res Commun. 2013;438(1):103-9. [3]Cutolo M, et al. Arthritis Res Ther. 2009;11:R176. [4]Pelegrin P., Surprenant, A. EMBO J. 2009 Jul 22; 28(14): 2114–2127. Samuele Tardito: None declared, Stefano Soldano: None declared, Emanuele Gotelli: None declared, Paola Montagna: None declared, Sabrina Paolino: None declared, Vanessa Smith: None declared, Maurizio Cutolo Grant/research support from: I received grant/research support from Bristol-Myers Squibb, Boehringer, Celgene.

Tropical cyclones are major disturbances for coastal systems. Hurricane Harvey made landfall in Texas, USA, on August 25, 2017 as a category 4 storm. There were two distinct disturbances associated with this storm that were spatially decoupled: (1) high winds causing direct damage and storm surge, and (2) high rains causing scouring floods and significant discharge of fresh water carrying carbon and nutrients to estuaries. Here, we provide a synthesis of the effects of Hurricane Harvey on biogeochemical, hydrographic, and biotic components of freshwater and estuarine systems and their comparative resistance and resilience to wind-and rain-driven disturbances. Wind-driven disturbances were most severe along the coastal barrier islands and lower estuaries, damaging mangroves and seagrass and increasing sediment coarseness. Rain-driven disturbances were most pronounced within freshwater streams and the upper estuaries. Large volumes of freshwater run-off reduced the abundance of riverine fauna and caused hypoxic and hyposaline conditions in the estuaries for over a week. In response to this freshwater input event, benthic fauna diversity and abundance decreased, but mobile fauna such as estuarine fishes did not markedly change. Although hydrographic and biogeochemical components were highly perturbed, they returned to baseline conditions within days. In contrast, biotic components demonstrated lower magnitude changes, but some of these organisms, particularly the sedentary flora and fauna, required weeks to months to return to pre-storm conditions, and some did not recover within the 6 months reported here. Our synthesis illustrates that resistance and resilience of system components may negatively co-vary and that structural components of coastal systems may be the most vulnerable to long-term changes following tropical cyclones.

  This Case Report presents the rehabilitation of a 66-year-old female patient using a telescopic retention system with Polyetheretherketone (PEEK) secondary caps. The treatment utilized PEEK-based conometric retention for a partial upper-arch prosthesis. The report highlights the advantages and disadvantages of this approach compared to traditional retention systems. The patient's initial concerns about removability and aesthetic functionality were alleviated, and her satisfaction was underscored by significant improvements in her social activities and oral comfort. The case illustrates the feasibility of integrating PEEK into telescopic systems, addressing limitations of traditional materials and telescopic coupling while providing a cost-effective. Further clinical evaluation and research into surface modifications are essential to fully optimize this approach for long-term success.

BackgroundPure autonomic failure (PAF) and multiple system atrophy (MSA) are both characterised by chronic dysautonomia although presenting different disability and prognosis. Skin autonomic function evaluation by indirect tests has revealed conflicting results in these disorders. Here, the authors report the first direct analysis of skin sympathetic fibres including structure and function in PAF and MSA to ascertain different underlying autonomic lesion sites which may help differentiate between the two conditions.MethodsThe authors studied eight patients with probable MSA (mean age 60±5 years) and nine patients fulfilling diagnostic criteria for PAF (64±8 years). They underwent head-up tilt test (HUTT), extensive microneurographic search for muscle and skin sympathetic nerve activities from peroneal nerve and punch skin biopsies from finger, thigh and leg to evaluate cholinergic and adrenergic autonomic dermal annexes innervation graded by a semiquantitative score presenting a high level of reliability.ResultsMSA and PAF patients presented a comparable neurogenic orthostatic hypotension during HUTT and high failure rate of microneurographic trials to record sympathetic nerve activity, suggesting a similar extent of chronic dysautonomia. In contrast, they presented different skin autonomic innervation in the immunofluorescence analysis. MSA patients showed a generally preserved skin autonomic innervation with a significantly higher score than PAF patients showing a marked postganglionic sympathetic denervation. In MSA patients with a long disease duration, morphological abnormalities and/or a slightly decreased autonomic score could be found in the leg reflecting a mild postganglionic involvement.ConclusionAutonomic innervation study of skin annexes is a reliable method which may help differentiate MSA from PAF.

The aims of this observational study are the following: to identify diagnosis and treatment strategies for Burning Mouth Syndrome (BMS) according to current literature; to compare data collected in a sample of patients suffering from BMS with the data reported in the literature; to highlight the role of the dentist in the management of BMS. A sample of 10 consecutively treated patients was recruited to fulfill the research inquiries. All patients received a BMS diagnosis and underwent medical and psychological therapy. The patients were asked to evaluate their pain levels before and after treatment, filling in a Visual Analogic Scale and a Numerical Pain Rating Scale (NRS) to rate to what extent the treatment had been successful. A literature review was conducted on Pubmed and Cochrane using different keyword combinations. In the study group, 9/10 patients declared that the therapy gave satisfactory results. 4/10 patients reported benefit from the prescription of Clonazepam. Twelve articles were selected in the literature review. The review of literature presented in this work does not offer unequivocal evidence of Burning Mouth Syndrome diagnosis and treatment. Results obtained from the sample of 10 patients cannot be considered useful evidence to establish a clinical protocol.

A theoretical underpinning of the standard model of fundamental particles and interactions is CPT invariance, which requires that the laws of physics be invariant under the combined discrete operations of charge conjugation, parity and time reversal. Antimatter, the existence of which was predicted by Dirac, can be used to test the CPT theorem—experimental investigations involving comparisons of particles with antiparticles are numerous 1 . Cold atoms and anti-atoms, such as hydrogen and antihydrogen, could form the basis of a new precise test, as CPT invariance implies that they must have the same spectrum. Observations of antihydrogen in small quantities and at high energies have been reported at the European Organization for Nuclear Research (CERN) 2 and at Fermilab 3 , but these experiments were not suited to precision comparison measurements. Here we demonstrate the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment. The neutral anti-atoms have been detected directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.