Seismic reliability-based design of hardening structures equipped with double sliding devices

This study deals with seismic reliability-based design (SRBD) relationships in terms of beha-vior factors and displacement demands for hardening structures equipped with double fric-tion pendulum system (DFPS) bearings. An equivalent 3dof system having a hardening post-yield slope is adopted to describe the superstructure behavior, whereas velocity-dependent laws are assumed to model the responses of the two surfaces of the DFPS. The yielding cha-racteristics of the superstructures are defined for increasing behavior factors in compliance with the seismic hazard of L’Aquila site (Italy) and with NTC18 assuming a lifetime of 50 years. Considering several natural seismic records and building properties under the hypo-thesis of modelling the friction coefficients of the two surfaces of the DFPS as random variables, incremental dynamic analyses are performed to evaluate the seismic fragility and the seismic reliability of these systems. Finally, seismic reliability is evaluated and seismic relia-bility-based design (SRBD) curves for the two surfaces of the double sliding devices are de-scribed

Urban ecosystem services: tree diversity and stability of tropospheric ozone removal

Urban forests provide important ecosystem services, such as urban air quality improvement by removing pollutants. While robust evidence exists that plant physiology, abundance, and distribution within cities are basic parameters affecting the magnitude and efficiency of air pollution removal, little is known about effects of plant diversity on the stability of this ecosystem service. Here, by means of a spatial analysis integrating system dynamic modeling and geostatistics, we assessed the effects of tree diversity on the removal of tropospheric ozone (O3) in Rome, Italy, in two years (2003 and 2004) that were very different for climatic conditions and ozone levels. Different tree functional groups showed complementary uptake patterns, related to tree physiology and phenology, maintaining a stable community function across different climatic conditions. Our results, although depending on the city-specific conditions of the studied area, suggest a higher function stability at increasing diversity levels in urban ecosystems. In Rome, such ecosystem services, based on published unitary costs of externalities and of mortality associated with O3, can be prudently valued to roughly US$2 and$3 million/year, respectively

Oncogenic Mutations of MYD88 and CD79B in Diffuse Large B-Cell Lymphoma and Implications for Clinical Practice

Simple SummaryA diagnosis of diffuse large B-cell lymphoma in our therapeutic era should be implemented by the definition of the cell of origin, additional immunohistochemistry (i.e., BCL2 and MYC), and by fluorescent in-situ hybridization. The next step, suggested by the seminary works we will discuss in this review, will be to implement the definition of sub-categories by the recognition of single gene mutations and pathways that may be targetable by newer drugs. We here describe the impact that MYD88 and CD79B activating mutations, two of the most frequent mutations in several DLBCL subtypes, may achieve in the next future in the diagnosis and therapeutics of such a relevant lymphoma subtype.Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in adults. Despite the recognition of transcriptional subtypes with distinct functional characteristics, patient outcomes have not been substantially altered since the advent of chemoimmunotherapy (CIT) twenty years ago. Recently, a few pivotal studies added to the disease heterogeneity by describing several activating mutations, which have been associated with disease presentation, B-cell function and behavior, and final outcome. DLBCL arises from antigen exposed B-cells, with the B-cell receptor (BCR) playing a central role. BCR-activity related mutations, such as CD79B and MYD88, are responsible for chronic activation of the BCR in a substantial subset of patients. These mutations, often coexisting in the same patient, have been found in a substantial subset of patients with immune-privileged (IP) sites DLBCLs, and are drivers of lymphoma development conferring tissue-specific homing properties. Both mutations have been associated with disease behavior, including tumor response either to CIT or to BCR-targeted therapy. The recognition of CD79B and MYD88 mutations will contribute to the heterogeneity of the disease, both in recognizing the BCR as a potential therapeutic target and in providing genetic tools for personalized treatment

Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis.

The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, we show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle-specific Cox15 knockout mouse (Cox15sm/sm ). Rapamycin treatment restored autophagic flux, which was impaired in naïve Cox15sm/sm muscle, and reduced the number of damaged mitochondria, which accumulated in untreated Cox15sm/sm mice. Conversely, rilmenidine, an mTORC1-independent autophagy inducer, was ineffective on the myopathic features of Cox15sm/sm animals. This stark difference supports the idea that inhibition of mTORC1 by rapamycin has a key role in the improvement of the mitochondrial function in Cox15sm/sm muscle. In contrast to rilmenidine, rapamycin treatment also activated lysosomal biogenesis in muscle. This effect was associated with increased nuclear localization of TFEB, a master regulator of lysosomal biogenesis, which is inhibited by mTORC1-dependent phosphorylation. We propose that the coordinated activation of autophagic flux and lysosomal biogenesis contribute to the effective clearance of dysfunctional mitochondria by rapamycin

Assessment of the Effects of Edible Microalgae in a Canine Gut Model

Microalgae are a source of bioactive compounds having recently been studied for their possible application as health-promoting ingredients. The aim of the study was to evaluate in an in vitro canine gut model the effects of four microalgae, Arthrospira platensis (AP), Haematococcus pluvialis (HP), Phaeodactylum tricornutum (PT) and Chlorella vulgaris (CV), on some fecal microbial populations and metabolites. The four microalgae were subjected to an in vitro digestion procedure, and subsequently, the digested biomass underwent colonic in vitro fermentation. After 6 h of incubation, PT increased propionate (+36%) and butyrate (+24%), and decreased total BCFA (-47%), isobutyrate (-52%) and isovalerate (-43%) and C. hiranonis (-0.46 log10 copies/75 ng DNA). After 24 h, PT increased propionate (+21%) and isovalerate (+10%), and decreased the abundance of Turicibacter spp. (7.18 vs. 6.69 and 6.56 log10 copies/75 ng DNA for CTRL vs. PT, respectively); moreover, after 24 h, CV decreased C. coccoides (-1.12 log10 copies/75 ng DNA) and Enterococcus spp. (-0.37 log10 copies/75 ng DNA). In conclusion, the microbial saccharolytic activities and the shift in fecal bacterial composition were less pronounced than expected, based on current literature. This study should be considered as a preliminary assessment, and future investigations are required to better understand the role of microalgae in canine nutrition

Extradural Peripheral Nerve Sheath Tumour at T7 Level in a 2-Year-Old Dog

The aim of this report is to describe an unusual localization of nerve sheath tumour (NST), clinical presentation, imaging, surgical management, and outcome in a 2-year- old dog. A 2-year-old female American Staffordshire Terrier presented with non- ambulatory paraparesis, thoracolumbar hyperaesthesia, hindlimb hyperreflexia, and mild muscle atrophy. Computed tomography and magnetic resonance imaging revealed an extradural mass at T7-T8, without vertebral lesions. Surgical treatment consisted in resection of the soft tissue mass through dorsal laminectomy. The dog was ambulatory within 24hours and free of recurrence at 18 months postoperatively. Histopathologic and features of immunohistochemistry were consistent with NST. The NST of this report was similar to those described before, but exhibited unusual characteristics, such as being extradural, without extension into intervertebral forami- na, and being located in an atypical region (T7-T8). Moreover, survival time and relapse- free interval are greater than previously reported for similar cases

Outcomes of Abrupt Switch to Bevacizumab of Patients Undergoing Aflibercept Intravitreal Injections for Neovascular Age-Related Macular Degeneration in a Tertiary Center in Lombardy, Italy: A Real-Life Retrospective Analysis

To assess real-life anatomical and functional outcomes of switch to bevacizumab in patients undergoing aflibercept intravitreal injections for nAMD

Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis

Abstract The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, we show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle‐specific Cox15 knockout mouse (Cox15sm/sm). Rapamycin treatment restored autophagic flux, which was impaired in naïve Cox15sm/sm muscle, and reduced the number of damaged mitochondria, which accumulated in untreated Cox15sm/sm mice. Conversely, rilmenidine, an mTORC1‐independent autophagy inducer, was ineffective on the myopathic features of Cox15sm/sm animals. This stark difference supports the idea that inhibition of mTORC1 by rapamycin has a key role in the improvement of the mitochondrial function in Cox15sm/sm muscle. In contrast to rilmenidine, rapamycin treatment also activated lysosomal biogenesis in muscle. This effect was associated with increased nuclear localization of TFEB, a master regulator of lysosomal biogenesis, which is inhibited by mTORC1‐dependent phosphorylation. We propose that the coordinated activation of autophagic flux and lysosomal biogenesis contribute to the effective clearance of dysfunctional mitochondria by rapamycin

Integration of epigenetic regulatory mechanisms in heart failure

The number of “omics” approaches is continuously growing. Among others, epigenetics has appeared as an attractive area of investigation by the cardiovascular research community, notably considering its association with disease development. Complex diseases such as cardiovascular diseases have to be tackled using methods integrating different omics levels, so called “multi-omics” approaches. These approaches combine and co-analyze different levels of disease regulation. In this review, we present and discuss the role of epigenetic mechanisms in regulating gene expression and provide an integrated view of how these mechanisms are interlinked and regulate the development of cardiac disease, with a particular attention to heart failure. We focus on DNA, histone, and RNA modifications, and discuss the current methods and tools used for data integration and analysis. Enhancing the knowledge of these regulatory mechanisms may lead to novel therapeutic approaches and biomarkers for precision healthcare and improved clinical outcomes

Is there a role in acute kidney injury for FGF23 and Klotho?

ABSTRACT Cardio-renal syndrome is a clinical condition that has recently been well defined. In acute kidney disease, this interaction might trigger chronic processes determining the onset of cardiovascular events and the progression of chronic kidney disease. Moreover, the high mortality rate of acute kidney injury (AKI) is also linked to the fact that this condition is often complicated by dysfunctions of other organs such as lungs or heart, or is associated with septic episodes. In this context the role and the potential link between bone, heart and kidney is becoming an important topic of research. The aim of this review is to describe the cardiac alterations in the presence of AKI (cardiorenal syndrome type 3) and explore how bone can interact with heart and kidney in determining and influencing the trend of AKI in the short and long term. The main anomalies of mineral metabolism in patients with AKI will be reported, with specific reference to the alterations of fibroblast growth factor 23 and Klotho as a link between the bone–kidney–heart axis