Haemodynamic Response to a Standard Meal: Consideration on A Case of Significant Blood Pressure Peaks in a Diabetic Hypertensive Patient Treated with ARB and Comparison with Normal Age and Sex Matched Subjects

A standard meal is a stimulus that produces a response that consists in the redistribution of blood flow to the splanchnic district, potentially, affecting systemic blood pressure, this phenomenon was studied in animal models and in critic patient. Here we report a case of a diabetic hypertensive-in-treatment woman where two significant blood pressure peaks were recorded, during lunch and dinner, over an optimal 24/h blood pressure control. In the absence of previous normal reference values in the literature, we retrieved a series of n=10 age and sex matched subjects diagnosed normotensive on the mean of 24/h Ambulatory Blood Pressure Monitoring. We finally present our considerations on the normal response to a standard meal compared to what was found in the literature and in the present case, where an impaired control of resistance is hypothesised, and on the possible mechanisms supporting

PDE5 inhibitors, erectile dysfunction and beyond : How, sometimes, indications are the consequences of marketing strategies and/or serendipity

Phosphodiesterase inhibitors (PDE5i) have an established role in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH) but, at the same time, they represent a paradigmatic example of a class of drugs, originally tested for a clinical indication, shifted to another one, for the unexpected emergence of strong evidences opening towards a new market, at that time still to be defined, but with an enormous potential. Sildenafil, the primer of PDE5i drugs patented in 1996, was designed and thought as anti-hypertensive/anginal, early relocated for ED and approved for this in 1998 despite emerging evidences of a further possible use, albeit numerically limited, in PAH. The apparent lack of interest in other fields of application continue at least until 2004 when, possibly, due to the upcoming of 2 new PDE5i on the market, the request for PAH, supported by a trial, was finally submitted and obtained by FDA in 2005. It is noteworthy that in medicine, when a relevant cellular mechanism is identified and targeted with a new drug, the results are not always predictable and/or are in agreement with the interests of the market but serendipity can help. Thus development/marketing of drugs is a multifactorial phenomenon that includes, also, potential/effectiveness of the molecules, beliefs/curiosity of the researchers, doctor/patient expectations, and, first of all, the economical interest related to their economic exploitation. In this review we wanted to explore the potentials, if any, of PDE5i beyond ED, by searching the literature for off-label applications

Anthropogenic fibers and microplastics in the pelagic gooseneck barnacle Lepas (Lepas) anatifera in Capo Milazzo Marine Protected Area (Tyrrhenian Sea): A first characterization

This study provides an assessment of the efficiency of the biofouler Lepas (Lepas) anatifera Linnaeus, 1758 in capturing microplastics and microfiber particles floating in the water column. In this context, we collected pelagic gooseneck barnacles at fixed moorings in the Capo Milazzo Marine Protected Area (MPA). Fibers and fragments were found in the digestive tract of 30% of the 120 specimens collected. The ingested debris were mainly fibers (85.9%) of synthetic (30.6%) and natural (11.7%) origin, with length ranging between 1 and 2 mm (33.3%) and transparent (47.2%). The highest concentration of fibers was recorded in barnacles collected in the western sector of the MPA that is more affected by the input of organic matter coming from several urban wastewaters. No correlation was found between the presence of artificial polymers in L. (Lepas) anatifera and the size of individuals. The great diversity of fibers and plastic fragments by typology, size, shape and color, as well as the large number of bivalve and ostracod shells found in the digestive tract of the samples, confirm the opportunistic diet of these organisms, which can indiscriminately ingest any type of prey and cannot distinguish between microplastics and food. The results obtained, as well as the wide distribution and abundance, and ease of sampling of these barnacle species in macrofouling suggest that including this species in monitoring programs could be a cost-effective and easy method for assessing the presence of microplastics and microfibers in coastal marine waters to monitor the ecological status of pelagic and coastal ecosystems, including MPAs

Epigenetic changes and nuclear factor-\u3baB activation, but not microRNA-224, downregulate Raf-1 kinase inhibitor protein in triple\u2011negative breast cancer SUM 159 cells

Raf-1 kinase inhibitor protein (RKIP) is a tumor suppressor and metastasis inhibitor, which enhances drug\u2011induced apoptosis of cancer cells. Downregulation of RKIP may be significant in the biology of highly aggressive and drug\u2011resistant tumors, for example triple\u2011negative breast cancers (TNBCs). Potential causes for the low levels of RKIP expressed by SUM 159 TNBC cells were investigated in the present study. Bisulphite modification, methylation specific\u2011polymerase chain reaction (PCR) and a TransAM NF-\u3baB assay were performed and the results suggested that various mechanisms, including methylation of the gene promoter, histone deacetylation and nuclear factor\u2011\u3baB (NF\u2011\u3baB) activation, but not targeting by microRNA\u2011224 (miR/miRNA\u2011224), as determined by transfection of pre\u2011miR\u2011224 miRNA precursor or anti\u2011miR\u2011224 miRNA inhibitor, may downregulate RKIP in these cells. Furthermore, reverse transcription\u2011quantitative PCR, western blotting,3\u2011(4,5\u2011dimethylthiazol\u20112\u2011yl)\u20115\u2011(3\u2011carboxymethoxyphenyl)\u20112\u2011(4\u2011sulphophenyl)\u20112H\u2011tetrazolium cell growth assay and flow cytometry revealed that in SUM 159 cells, the demethylating agent 5\u2011aza\u20112'\u2011deoxycytidine (5\u2011AZA), the histone deacetylase inhibitor trichostatin A (TSA) and the NF\u2011\u3baB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) enhanced RKIP expression and resulted in significant cell growth inhibition and induction of apoptosis. 5\u2011AZA and TSA mainly produced additive antitumor effects, while the combination of DHMEQ and TSA exhibited significant synergy in cell growth inhibition and induction of apoptosis assays. Increasing evidence that aberrant activation of NF\u2011\u3baB signaling is a frequent characteristic of TNBC highlights the fact that this transcription factor may be a useful target for treatment of such tumors. In addition to DHMEQ, proteasome inhibitors may also represent valuable therapeutic resources in this context. Notably, proteasome inhibitors, in addition to the inhibition of NF\u2011\u3baB activation, may also restore RKIP levels by inhibiting proteasome degradation of the ubiquitinated protein. The current results contribute to the understanding of the molecular mechanisms of RKIP downregulation in TNBC and suggest possible novel therapeutic approaches for the treatment of these types of cancer

Atrial fibrillation, an epiphenomenon of acute Stanford type-A aortic dissection with suspected intimo-intimal intussusception

Key Clinical Message Supraventricular arrhythmias can sometimes be only epiphenomena appearing during acute hypoxia, pneumonia, pulmonary embolism, and thrombosis. Indeed, atrial fibrillation is not rare in acute aortic dissection as it is estimated in about one half of patients and may be secondary to a perfusion deficit of the sinoatrial node artery

The value of the multidisciplinary team in metastatic renal cell carcinoma: paving the way for precision medicine in toxicities management

The new landscape of treatments for metastatic clear cell renal carcinoma (mRCC) is constantly expanding, but it is associated with the emergence of novel toxicities, adding to up to those observed in the tyrosine-kinase inhibitor (TKI) era. Indeed, the introduction of immune checkpoint inhibitors (ICIs) alone or in combination has been associated with the development of immune-related adverse events (irAEs) involving multiple-organ systems which, even if rarely, had led to fatal outcomes. Moreover, due to the relatively recent addition of ICIs to the previously available treatments, the potential additive adverse effects of these combinations are still unknown. A prompt recognition and management of these toxicities currently represents a fundamental issue in oncology, since it correlates with the outcome of cancer patients. Even if clinical guidelines provide indications for the management of irAEs, no specific protocol to evaluate the individual risk of developing an adverse event during therapy is currently available. A multidisciplinary approach addressing appropriate interventions aimed at reducing the risk of any insidious, severe, and/or dose-limiting toxicity might represent the most efficacious strategy to timely prevent and manage severe irAEs, allowing indirectly to improve both patients' cancer-specific survival and quality of life. In this review, we reported a five-case series of toxicity events that occurred at our center during treatment for mRCC followed by the remarks of physicians from different specialties, pinpointing the relevant role of an integrated and extended multidisciplinary team in a modern model of mRCC patient management

Fenomeno Caulerpa 2010-2013. Rapporto sull'evoluzione delle specie aliene nel Canale di Sicilia

Gli studi effettuati da ARPA-Sicilia, ISPRA e CNR-IAMC hanno perseguito l’obiettivo principale di monitorare e valutare l’impatto della diffusione delle alghe indagate, attraverso l’analisi dell’evoluzione spazio-temporale del fenomeno e la caratterizzazione eco-tossicologica delle aree di pesca maggiormente interessate dalla presenza delle caulerpe. In particolare Le ricerche di ARPA-Sicilia sono state mirate a: - Definire le aree di studio principalmente interessate dal fenomeno di diffusione delle due alghe aliene; - Caratterizzare da un punto di vista ambientale le aree oggetto d’indagine; - Valutare le pressioni antropiche che insistono lungo le coste delle aree indagate; - Stimare l’influenza che le pressioni antropiche possono esercitare sulla diffusione della Caulerpa; - Indagare l’andamento spazio-temporale della distribuzione di Caulerpa in specifiche aree di indagine. Gli studi condotti da ISPRA hanno puntato a: - Valutare possibili interferenze dell’alga con le attività di pesca, l’intasamento delle reti e la riduzione della pescabilità dell’attrezzo; - Rilevare l’eventuale diversità tra aree con insediamento e prive di insediamento; - Avviare l’introduzione di buone pratiche per evitare che la pesca possa rappresentare un ulteriore vettore di invasioni secondarie attraverso disseminazione dei frammenti e propaguli dell’alga; - Definire comportamenti alieutici nel tempo utili alla mitigazione del potenziale impatto della pesca sulle risorse nelle aree colpite; - Istituire in tutta l’area di studio e, in particolare, nell’arcipelago delle Pelagie, un “Osservatorio delle Specie Aliene” per svolgere attività di monitoraggio sulla diffusione delle specie aliene, al fine di formulare proposte gestionali mirate alla salvaguardia degli ecosistemi e delle attività economiche di pesca. Le indagini realizzate dal CNR-IAMC hanno avuto come obiettivi principali: - Confrontare le caratteristiche dei popolamenti bentonici associati a praterie di Posidonia oceanica della Sicilia meridionale interessate dall’invasione di Caulerpa taxifolia var. distichophylla con quelle di popolamenti associati a posidonieti di località limitrofe non colpite dal fenomeno; - Confrontare la struttura trofica della comunità bentonica associata a matte di Posidonia oceanica in località invase e non invase da alghe aliene del genere Caulerpa della Sicilia meridionale; - Valutare gli effetti dell’invasione di Caulerpa racemosa var. cylindracea sulla struttura e sulla funzione di popolamenti macrobentonici sessili di fondo duro dell’infralitorale

Uncoupling the functions of CALM in VAMP sorting and clathrin-coated pit formation.

CALM (clathrin assembly lymphoid myeloid leukemia protein) is a cargo-selective adaptor for the post-Golgi R-SNAREs VAMPs 2, 3, and 8, and it also regulates the size of clathrin-coated pits and vesicles at the plasma membrane. The present study has two objectives: to determine whether CALM can sort additional VAMPs, and to investigate whether VAMP sorting contributes to CALM-dependent vesicle size regulation. Using a flow cytometry-based endocytosis efficiency assay, we demonstrate that CALM is also able to sort VAMPs 4 and 7, even though they have sorting signals for other clathrin adaptors. CALM homologues are present in nearly every eukaryote, suggesting that the CALM family may have evolved as adaptors for retrieving all post-Golgi VAMPs from the plasma membrane. Using a knockdown/rescue system, we show that wild-type CALM restores normal VAMP sorting in CALM-depleted cells, but that two non-VAMP-binding mutants do not. However, when we assayed the effect of CALM depletion on coated pit morphology, using a fluorescence microscopy-based assay, we found that the two mutants were as effective as wild-type CALM. Thus, we can uncouple the sorting function of CALM from its structural role

Aiding Planning in Air Traffic Control: An Experimental Investigation of the Effects of Perceptual Information Integration

Prior research examined how controllers plan in their traditional environment and identified various information uncertainties as detriments to planning. A planning aid was designed to reduce this uncertainty by perceptually representing important constraints. This included integrating spatial information on the radar screen with discrete information (planned sequences of air traffic). Previous research reported improved planning performance and decreased workload in the planning aid condition. The purpose of this paper was to determine the source of these performance improvements. Analysis of computer interactions using loglinear modeling showed that the planning interface led to less repetitive - but more integrated - information retrieval compared with the traditional planning environment. Ecological interface design principles helped explain how the integrated information retrieval gave rise to the performance improvements. Actual or potential applications of this research include the design and evaluation of interface automation that keeps users in active control by modification of perceptual task characteristics.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline