Functioning issues in inpatients affected by COVID-19-related moderate pulmonary impairment: a real-practice observational study

Objective To investigate the correlations between clinical, functional, and radiological outcomes in inpatients with coronavirus disease 2019 (COVID-19). Methods In this observational study, we recruited inpatients affected by moderate COVID-19 disease. The clinical evaluation comprised the Cumulative Illness Rating Scale (CIRS), numerical rating scale (NRS), modified Rankin scale (mRS), and the modified Borg dyspnea scale (mBDS). Respiratory involvement was assessed with computed tomography (CT) and graded with a CT-severity score (CT-SS). We retrospectively assessed functioning using the International Classification of Functioning, Disability and Health (ICF) codes of the Clinical Functioning Information Tool (ClinFIT) COVID-19 in the acute phase. Correlation analysis was performed 1) between clinical, instrumental, and functional parameters and 2) between ICF categories. Results The data showed statistically significant moderate correlations between CT-SS and the following categories: b152 “emotional functions” and b440 “respiratory functions”. Conclusion This is the first study to use the ICF framework in people with a moderate form of COVID-19 in the acute phase. Considering the correlations between some ICF categories and radiological findings, our results support the use of the ClinFIT COVID-19 for a comprehensive assessment of COVID-19 patients

Post-Messinian evolutionary relationships across the Sicilian channel: Mitochondrial and nuclear markers link a new green toad from Sicily to African relatives

<p>Abstract</p> <p>Background</p> <p>Little attention has been paid to the consequences of the last landbridge between Africa and Sicily on Mediterranean biogeography. Previous paleontological and scarce molecular data suggest possible faunal exchange later than the well-documented landbridge in the Messinian (5.3 My); however, a possible African origin of recent terrestrial Sicilian fauna has not been thoroughly tested with molecular methods. To gain insight into the phylogeography of the region, we examine two mitochondrial and two nuclear markers (one is a newly adapted intron marker) in green toads (<it>Bufo viridis </it>subgroup) across that sea barrier, the Strait of Sicily.</p> <p>Results</p> <p>Extensive sampling throughout the western Mediterranean and North Africa revealed a deep sister relationship between Sicilian (<it>Bufo siculus </it>n.sp.) and African green toads (<it>B. boulengeri</it>) on the mitochondrial and nuclear level. Divergence times estimated under a Bayesian-coalescence framework (mtDNA control region and 16S rRNA) range from the Middle Pliocene (3.6 My) to Pleistocene (0.16 My) with an average (1.83 to 2.0 My) around the Pliocene/Pleistocene boundary, suggesting possible land connections younger than the Messinian (5.3 My). We describe green toads from Sicily and some surrounding islands as a new endemic species (<it>Bufo siculus</it>). <it>Bufo balearicus </it>occurs on some western Mediterranean islands (Corsica, Sardinia, Mallorca, and Menorca) and the Apennine Peninsula, and is well differentiated on the mitochondrial and nuclear level from <it>B. siculus </it>as well as from <it>B. viridis </it>(Laurenti), whose haplotype group reaches northeastern Italy, north of the Po River. Detection of Calabrian <it>B. balearicus </it>haplotypes in northeastern Sicily suggests recent invasion. Our data agree with paleogeographic and fossil data, which suggest long Plio-Pleistocene isolation of Sicily and episodic Pleistocene faunal exchange across the Strait of Messina. It remains unknown whether both species (<it>B. balearicus, B. siculus</it>) occur in sympatry in northern Sicily.</p> <p>Conclusion</p> <p>Our findings on green toads give the first combined mitochondrial and nuclear sequence evidence for a phylogeographic connection across the Strait of Sicily in terrestrial vertebrates. These relationships may have implications for comparative phylogeographic research on other terrestrial animals co-occurring in North Africa and Sicily.</p

SARS-CoV-2 Infection as a Determining Factor to the Precipitation of Ischemic Priapism in a Young Patient with Asymptomatic COVID-19

COVID-19 is a disease characterized by respiratory distress, systemic inflammation, multiple organ dysfunction and coagulation disorders, chiefly pulmonary embolism, and deep venous thrombosis. In this case report, we discuss a peculiar case of ischemic priapism in a 36-year-old patient with asymptomatic COVID-19 and no other plausible causes of thrombophilia and/or alternative causes of priapism, as well as discussing possible explanations for such remarkable findings and comparing them to analogous cases recorded in literature. The patient was unsuccessfully treated via cavernous blood aspiration and required several shunting procedures, with no further recurrences and negative testing for pulmonary embolism, deep venous thrombosis, and other causes of thrombophilia

IGF-I induces upregulation of DDR1 collagen receptor in breast cancer cells by suppressing MIR-199a-5p through the PI3K/AKT pathway.

Discoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that contributes to epithelial-to-mesenchymal transition and enhances cancer progression. Our previous data indicate that, in breast cancer cells, DDR1 interacts with IGF-1R and positively modulates IGF-1R expression and biological responses, suggesting that the DDR1-IGF-IR cross-talk may play an important role in cancer.In this study, we set out to evaluate whether IGF-I stimulation may affect DDR1 expression. Indeed, in breast cancer cells (MCF-7 and MDA-MB-231) IGF-I induced significant increase of DDR1 protein expression, in a time and dose dependent manner. However, we did not observe parallel changes in DDR1 mRNA. DDR1 upregulation required the activation of the PI3K/AKT pathway while the ERK1/2, the p70/mTOR and the PKC pathways were not involved. Moreover, we observed that DDR1 protein upregulation was induced by translational mechanisms involving miR-199a-5p suppression through PI3K/AKT activation. This effect was confirmed by both IGF-II produced by cancer-associated fibroblasts from human breast cancer and by stable transfection of breast cancer cells with a human IGF-II expression construct. Transfection with a constitutively active form of AKT was sufficient to decrease miR-199a-5p and upregulate DDR1. Accordingly, IGF-I-induced DDR1 upregulation was inhibited by transfection with pre-miR-199a-5p, which also impaired AKT activation and cell migration and proliferation in response to IGF-I.These results demonstrate that, in breast cancer cells, a novel pathway involving AKT/miR-199a-5p/DDR1 plays a role in modulating IGFs biological responses. Therefore, this signaling pathway may represent an important target for breast cancers with over-activation of the IGF-IR axis

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer

Impact of COVID-19 Pandemic on Children and Adolescents with Neuropsychiatric Disorders: Emotional/Behavioral Symptoms and Parental Stress

The objective of our study was to evaluate the impact of the COVID-19 pandemic on the emotional and behavioral symptoms in minors with neuropsychiatric disorders and on parental stress through a standardized neuropsychological assessment, comparing the data collected before the pandemic with those collected during the lock-down. Another goal of our study was to analyze the relationship between parental stress and behavioral/emotional symptoms in children. Our study was conducted on 383 families of patients who had already been referred at the Child Neuropsychiatry Unit of the University Hospital of Salerno for different neuropsychiatric conditions. All the parents completed two neuropsychological standardized questionnaires for the assessment of parental stress (PSI—Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour CheckList). The data collected during the pandemic were compared with those collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice. The comparison between the mean scores of PSI and CBCL before and after the pandemic showed a statistically significant increase in all subscales analyzed in the total sample. The correlation analysis showed significant positive relationship between the subscale Total Stress of PSI and the subscales Total Problems and Internalizing Problems of CBCL. Our study suggested that the COVID-19 pandemic and the corresponding measures adopted led to an increase in internalizing and externalizing symptoms in children and adolescents with neuropsychiatric disorder. Similarly, parental stress increased during COVID-19 and ahigher level of stress in parents can be related to the internalizing symptoms of their children

Progranulin Oncogenic Network in Solid Tumors

Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In addition, progranulin regulates the tumor microenvironment, affects the function of cancer-associated fibroblasts, and modulates tumor immune surveillance. However, the molecular mechanisms of progranulin oncogenic function are not fully elucidated. In bladder cancer, progranulin action relies on the activation of its functional signaling receptor EphA2. Notably, more recent data suggest that progranulin can also modulate a functional crosstalk between multiple receptor-tyrosine kinases, demonstrating a more complex and context-dependent role of progranulin in cancer. Here, we will review what is currently known about the function of progranulin in tumors, with a focus on its molecular mechanisms of action and regulation

Ram pressure feeding super-massive black holes

When supermassive black holes at the center of galaxies accrete matter (usually gas), they give rise to highly energetic phenomena named Active Galactic Nuclei (AGN). A number of physical processes have been proposed to account for the funneling of gas towards the galaxy centers to feed the AGN. There are also several physical processes that can strip gas from a galaxy, and one of them is ram pressure stripping in galaxy clusters due to the hot and dense gas filling the space between galaxies. We report the discovery of a strong connection between severe ram pressure stripping and the presence of AGN activity. Searching in galaxy clusters at low redshift, we have selected the most extreme examples of jellyfish galaxies, which are galaxies with long tentacles of material extending for dozens of kpc beyond the galaxy disk. Using the MUSE spectrograph on the ESO Very Large Telescope, we find that 6 out of the 7 galaxies of this sample host a central AGN, and two of them also have galactic-scale AGN ionization cones. The high incidence of AGN among the most striking jellyfishes may be due to ram pressure causing gas to flow towards the center and triggering the AGN activity, or to an enhancement of the stripping caused by AGN energy injection, or both. Our analysis of the galaxy position and velocity relative to the cluster strongly supports the first hypothesis, and puts forward ram pressure as another, yet unforeseen, possible mechanism for feeding the central supermassive black hole with gas.Comment: published in Nature, Vol.548, Number 7667, pag.30

D3.2 - Stato dell'infrastruttura 3DLab-Sicilia alla fine del periodo di sperimentazione in ambito di laboratorio

Questo rapporto presenta lo stato dell’infrastruttura 3DLab-Sicilia con particolare attenzione sullo stato di avanzamento della realizzazione dei tre laboratori nei nodi del progetto che compongono il Centro di Realtà Virtuale geograficamente distribuito e sulle sequenze (pipeline) di esecuzione di software implementate internamente per la creazione di modelli tridimensionali e scenari immersivi e offerte dal progetto a tutti i possibili utilizzatori esterni. Il documento è organizzato come segue: la Sezione 2 introduce lo stato dell’arte relativamente alle soluzioni di Cross Reality (XR, che comprende anche la Realtà Virtuale); la Sezione 3 presenta le caratteristiche e le potenzialità del Centro di Realtà Virtuale di 3DLab-Sicilia; la Sezione 4 presenta gli ulteriori elementi chiave dell’infrastruttura che il progetto mette a disposizione dell’utenza; infine, nelle sezioni 5 e 6 vengono forniti i dettagli delle pipeline software supportate, rispettivamente, per servizi di utilità generale e per servizi specifici per gli use case del progetto

GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment

The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells. We analyzed gene expression data from published studies representing almost 5000 breast cancer patients to investigate whether GPER and IGF1 signaling establish an angiocrine gene signature in breast cancer patients. Next, we used GPER-positive but estrogen receptor (ER)-negative primary CAF cells derived from patient breast tumours and SKBR3 breast cancer cells to investigate the role of GPER in the regulation of VEGF expression and angiogenesis triggered by IGF1. We performed gene expression and promoter studies, western blotting and immunofluorescence analysis, gene silencing strategies and endothelial tube formation assays to evaluate the involvement of the HIF-1α/GPER/VEGF signaling in the biological responses to IGF1. We first determined that GPER is co-expressed with IGF1R and with the vessel marker CD34 in human breast tumors (n = 4972). Next, we determined that IGF1/IGF1R signaling engages the ERK1/2 and AKT transduction pathways to induce the expression of HIF-1α and its targets GPER and VEGF. We found that a functional cooperation between HIF-1α and GPER is essential for the transcriptional activation of VEGF induced by IGF1. Finally, using conditioned medium from CAFs and SKBR3 cells stimulated with IGF1, we established that HIF-1α and GPER are both required for VEGF-induced human vascular endothelial cell tube formation. These findings shed new light on the essential role played by GPER in IGF1/IGF1R signaling that induces breast tumor angiogenesis. Targeting the multifaceted interactions between cancer cells and tumor microenvironment involving both GPCRs and growth factor receptors has potential in future combination anticancer therapies