The occurrence of the stilbene piceatannol in grapes

Piceatannol (trans-3,3',4,5'-tetrahydroxy-stilbene) is a natural stilbene occurring in a number of plant species, and it has been shown to have beneficial effects on human health. The compound can seldom be consumed by humans, because it occurs in non-food plants, or in non-edible organs. Here we show for the first time that grapes (Vitis vinifera L. cv. Cabernet Sauvignon) have significant amounts of piceatannol (0.052 µg g-1 fresh wt). The identity of piceatannol was confirmed by HPLC and LC-MS.

Assessing the Impact of Different Ocean Analysis Schemes on Oceanic and Underwater Acoustic Predictions

Assimilating oceanic observations into prediction systems is an advantageous approach for real-time ocean environment characterization. However, its benefits to underwater acoustic predictions are not trivial due to the nonlinearity and sensitivity of underwater acoustic propagation to small-scale oceanic features. In order to assess the potential of oceanic data assimilation, integrated ocean-acoustic Observing System Simulation Experiments are conducted. Synthetic altimetry and in situ data were assimilated through a variational oceanographic data assimilation system. The predicted sound speed fields are then ingested in a range-dependent acoustic model for transmission loss (TL) predictions. The predicted TLs are analyzed for the purpose of (i) evaluating the contributions of different sources to the uncertainties of oceanic and acoustic forecasts and (ii) comparing the impact of different oceanic analysis schemes on the TL prediction accuracy. Using ensemble member clustering techniques, the contributions of boundary conditions, ocean parameterizations, and geoacoustic characterization to acoustic prediction uncertainties are addressed. Subsequently, the impact of three-dimensional variational (3DVAR), 4DVAR, and hybrid ensemble-3DVAR data assimilation on acoustic TL prediction at two signal frequencies (75 and 2,500 Hz) and different ranges (30 and 60 km) are compared. 3DVAR significantly improves the predicted TL accuracy compared to the control run. Promisingly, 4DVAR and hybrid data assimilation further improve the TL forecasts, the hybrid scheme achieving the highest skill scores for all cases, while being the most computationally intensive scheme. The optimal scheme choice thus depends on requirements on the accuracy and computational constraints. These findings foster developments of coupled data assimilation for operational underwater acoustic propagation

Internal tides in the central Mediterranean Sea: observational evidence and numerical studies

Internal tides are studied in the central Mediterranean Sea using observational data and numerical experiments. Both numerical results and observations indicate that the baroclinic variability in this area is dominated by the K1 diurnal tide. In agreement with previous studies, the diurnal internal tides have the characteristics of Kelvin-like bottom trapped waves. They are mainly generated by the interaction of the induced barotropic tidal flow with the steep bathymetric gradient connecting the Ionian Sea with the shallow Sicily Channel. The bathymetric gradient appears to be the major forcing shaping the propagation paths of the internal tides. The most energetic internal tides follow the steep bathymetric gradient, propagating southward and tending to dissipate rapidly. Other waves cross the continental shelf south of Malta and then split with one branch moving toward the southern coast of Sicily and the other moving toward the west. Internal tides propagate with a variable phase velocity of about 1 ms(-1) and a wavelength of the order of 100 km. During their journey, the internal waves appear to be subject to local processes that can modify their characteristics. The induced vertical shear strongly dominates the vertical turbulence and generates vertical mixing that alters the properties of the water masses traversing the area. Barotropic and internal tides remove heat from the ocean surface, increasing atmospheric heating, and redistributing energy through increased lateral heat fluxes. Lateral heat fluxes are significantly greater in the presence of internal tides due to the simultaneous increase in volume fluxes and water temperatures

In vivo effect of an immunostimulating bacterial lysate on human B lymphocytes.

The aim of the present study is to investigate in humans the mechanism by which the oral vaccine Polyvalent Mechanical Bacterial Lysate (PMBL) can rapidly mobilize specific immune response and evaluate the efficacy of its immunostimulating activity in preventing recurrent infections of the upper respiratory tract (URTIs) in a group of patients with a medical history of URTI recurrence. Patients received, by sublingual route, PBML, an immunostimulating lysate obtained by mechanical lysis of the most common bacteria responsible for upper respiratory tract infections. The treatment was administered for 10 consecutive days/month for 3 consecutive months. After the end of the treatment period the patients were followed up for an additional 3 months. The frequency of IgM memory B cells and the expression of the activation marker CD25 in peripheral blood lymphocytes were measured using the flow cytometric method before the start and at days 30 and 90 of the treatment cycle. To correlate clinical results to immunological parameters, the patients were monitored at different time-points during the treatment and at the end of follow-up period. The results showed that PMBL exerts a therapeutic and preventing effect in acute and recurrent infections of the upper respiratory tract and that this effect correlated with the activation and enhancement of both IgM memory B lymphocytes (CD24+/CD27+ cells) and IL2 receptor-expressing lymphocytes (CD25+ cells) involved either in humoral or cellular immunity

Patterns of genomic instability in gastric cancer: clinical implications and perspectives.

In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to the transcriptional silencing of various genes in gastric carcinogenesis. Intriguingly, more recently in addition to CpG island hypermethylation, a global DNA demethylation, that precedes genomic damage, has been observed in GC. Thus, epigenetic alterations may play a relevant role in gastric carcinogenesis as alternative mechanisms. Evidence suggests that although MSI, CIN and CIMP phenotypes can be distinguished from one another, there might be some degree of overlap. This review describes our current knowledge of the instability pathways in gastric carcinogenesis and the potential clinical applications for different forms of genomic instability in GC

Patterns of genomic instability in gastric cancer: clinical implications and perspectives

In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to the transcriptional silencing of various genes in gastric carcinogenesis. Intriguingly, more recently in addition to CpG island hypermethylation, a global DNA demethylation, that precedes genomic damage, has been observed in GC. Thus, epigenetic alterations may play a relevant role in gastric carcinogenesis as alternative mechanisms. Evidence suggests that although MSI, CIN and CIMP phenotypes can be distinguished from one another, there might be some degree of overlap. This review describes our current knowledge of the instability pathways in gastric carcinogenesis and the potential clinical applications for different forms of genomic instability in G

Ribozyme-mediated compensatory induction of menin-oncosuppressor function in primary fibroblasts from MEN1 patients

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Update on the pathogenesis and genetics of Paget's disease of bone

Studies over the past two decades have led to major advances in the pathogenesis of Paget's disease of bone (PDB) and particularly on the role of genetic factors. Germline mutations of different genes have been identified, as a possible cause of this disorder, and most of the underlying pathways are implicated in the regulation of osteoclast differentiation and function, whereas other are involved in cell autophagy mechanisms. In particular, about 30 different germline mutations of the Sequestosome 1 gene (SQSTM1) have been described in a significant proportion of familial and sporadic PDB cases. The majority of SQSTM1 mutations affect the ubiquitin-binding domain of the protein and are associated to a more severe clinical expression of the disease. Also, germline mutations in the ZNF687 and PFN1 genes have been associated to severe, early onset, polyostotic PDB with increased susceptibly to neoplastic degeneration, particularly giant cell tumor. Mutations in the VCP (Valosin Containing Protein) gene cause the autosomal dominant syndrome "Inclusion Body Myopathy, PDB, Fronto-temporal Dementia," characterized by pagetic manifestations, associated with myopathy, amyotrophic lateral sclerosis and fronto-temporal dementia. Moreover, germline mutations in the TNFRSF11A gene, which encodes for RANK, were associated with rare syndromes showing some histopathological, radiological, and clinical overlap with PDB and in two cases of early onset PDB-like disease. Likewise, genome wide association studies performed in unrelated PDB cases identified other potential predisposition genes and/or susceptibility loci. Thus, it is likely that polygenic factors are involved in the PDB pathogenesis in many individuals and that modifying genes may contribute in refining the clinical phenotype. Moreover, the contribution of somatic mutations of SQSTM1 gene and/or epigenetic mechanisms in the pathogenesis of skeletal pagetic abnormalities and eventually neoplastic degeneration, cannot be excluded. Indeed, clinical and experimental observations indicate that genetic susceptibility might not be a sufficient condition for the clinical development of PDB without the concomitant intervention of viral infection, in primis paramixoviruses, and/or other environmental factors (e.g., pesticides, heavy metals or tobacco exposure), at least in a subset of cases. This review summarizes the most important advances that have been made in the field of cellular and molecular biology PDB over the past decades. © 2022 Gennari, Rendina, Merlotti, Cavati, Mingiano, Cosso, Materozzi, Pirrotta, Abate, Calabrese and Falchetti

Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation. © 2022 by the authors