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

The Dietary Intake of Polyphenols Is Associated with a Lower Risk of Severe Lumbar Spinal Stenosis: A Case-Control Analysis from the PREFACE Study

Polyphenols are naturally occurring compounds endowed with antioxidant and anti-inflammatory properties. We sought to examine the association of dietary polyphenols with the risk of severe lumbar spinal stenosis (LSS), a condition possibly characterized by a high inflammatory component. A case-control study included 156 patients with LSS and indication to surgery and 312 controls, matched (1:2) for sex, age (±6 months), and physical activity. The polyphenol intake was calculated by matching food consumption data from a 188-item food frequency questionnaire with the Phenol-Explorer database regarding the polyphenol content of each reported food. In a multivariable-adjusted logistic regression analysis including lifestyles, sociodemographic factors, and the Mediterranean Diet Score, a 1-standard deviation (SD) increase in dietary polyphenols intake was associated with lower odds of LSS (Odds ratio [OR] = 0.65; 95% CI: 0.47–0.89). Analyses of different polyphenol classes showed that a per 1-SD in the consumption of flavonoids and stilbenes was related to lower LSS risk (OR = 0.57; 95% CI: 0.42–0.78; OR = 0.40; 95% CI: 0.27–0.61, respectively). Further adjustment for the total dietary antioxidant capacity did not modify the strength of these associations. A diet rich in polyphenols is independently associated with a lower risk of severe LSS, possibly through mechanisms that include the anti-inflammatory potential of these bioactive compounds

A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset

Background: Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits. Case presentation: In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment. Conclusions: The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL

Heme catabolism by tumor-associated macrophages controls metastasis formation

Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80hiCD115hiC3aRhiCD88hi), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80+HO-1+ bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1–CSF1R–C3aR axis. Inhibition of F4/80+HO-1+ TAM recruitment or myeloid-specific deletion of HO-1 blocks metastasis formation and improves anticancer immunotherapy. Relative expression of HO-1 in peripheral monocyte subsets, as well as in tumor lesions, discriminates survival among metastatic melanoma patients. Overall, these results identify a distinct cancer-induced HO-1+ myeloid subgroup as a new antimetastatic target and prognostic blood marker

An ensemble of eddy-permitting global ocean reanalyses from the MyOcean project

A set of four eddy-permitting global ocean reanalyses produced in the framework of the MyOcean project have been compared over the altimetry period 1993–2011. The main differences among the reanalyses used here come from the data assimilation scheme implemented to control the ocean state by inserting reprocessed observations of sea surface temperature (SST), in situ temperature and salinity profiles, sea level anomaly and sea-ice concentration. A first objective of this work includes assessing the interannual variability and trends for a series of parameters, usually considered in the community as essential ocean variables: SST, sea surface salinity, temperature and salinity averaged over meaningful layers of the water column, sea level, transports across pre-defined sections, and sea ice parameters. The eddy-permitting nature of the global reanalyses allows also to estimate eddy kinetic energy. The results show that in general there is a good consistency between the different reanalyses. An intercomparison against experiments without data assimilation was done during the MyOcean project and we conclude that data assimilation is crucial for correctly simulating some quantities such as regional trends of sea level as well as the eddy kinetic energy. A second objective is to show that the ensemble mean of reanalyses can be evaluated as one single system regarding its reliability in reproducing the climate signals, where both variability and uncertainties are assessed through the ensemble spread and signal-to-noise ratio. The main advantage of having access to several reanalyses differing in the way data assimilation is performed is that it becomes possible to assess part of the total uncertainty. Given the fact that we use very similar ocean models and atmospheric forcing, we can conclude that the spread of the ensemble of reanalyses is mainly representative of our ability to gauge uncertainty in the assimilation methods. This uncertainty changes a lot from one ocean parameter to another, especially in global indices. However, despite several caveats in the design of the multi-system ensemble, the main conclusion from this study is that an eddy-permitting multi-system ensemble approach has become mature and our results provide a first step towards a systematic comparison of eddy-permitting global ocean reanalyses aimed at providing robust conclusions on the recent evolution of the oceanic state

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Therapeutic Strategies in HCC: Radiation Modalities

Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment