Dynamic thiol/disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer

Thiol groups are important anti-oxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species (ROS). The aim of our study is to evaluate thiol–disulphide homeostasis with a novel recent automated method in patients with localized prostate cancer (PC) before and six months after radical prostatectomy (RP). 18 patients with PC and 17 healthy control subjects were enrolled into the study. Blood samples were collected from the controls subjects and patients before and six months after RP. Thiol–disulphide homeostasis was determined using a recently developed novel method. Prostate-specific antigen (PSA), albumin, total protein, total thiol, native thiol, disulphide and total antioxidant status (TAS) were measured and compared between the groups. Native thiol, total thiol and TAS levels were significantly higher in the control group than the patients before RP (p <.001). There was a non-significant increase in the native thiol, total thiol and TAS levels in the patients six months after RP in comparison to the levels before RP (p values.3,.3 and.09, respectively). We found a significant negative correlation between PSA and thiol levels. Our study demonstrated that the decreased thiol and TAS levels weakened anti-oxidant defence mechanism in the patients with PC as indicated. Increased oxidative stress in prostate cancer patients may cause metabolic disturbance and have a role in the aetiopathogenesis of prostate cancer

In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid.

BACKGROUND: hyaluronic acid (HA), a non-sulphated glycosaminoglycan, is present in synovial fluid, vitreous humour serum and many connective tissues. Pharmaceutical preparations of HA are used in clinical practice for wound healing, joint pain, kerato-conjunctivitis, asthma, mouth care, oesophageal-reflux, and gastritis. Moreover, it is used as a filler to counteract ageing and facial lipoatrophy. Our study aims at investigating the in vitro antiviral activity of a high molecular weight HA.METHODS: the MTT test was used to rule out the potential toxic effects of HA on the different cell lines used in the antiviral assays. The antiviral activity of HA against Coxsackievirus B5, Herpes simplex virus-1, Mumps virus, Adenovirus-5, Influenza Virus A/H1N1, Human Herpesvirus-6, Porcine Parvovirus, Porcine Reproductive and Respiratory Syndrome Virus was assessed by virus yield assays.RESULTS: the most effective inhibition was observed against Coxsackievirus B5, with 3Log reduction of the virus yield at 4mg/ml, and a reduction of 3.5Log and 2Log, at 2mg/ml and 1mg/ml, respectively: the selectivity index was 16. Mumps virus was highly inhibited too showing a reduction of 1.7Log at 1mg/ml and 1Log at 4mg/ml and 2mg/ml (selectivity index = 12). The selectivity index for Influenza Virus was 12 with the highest inhibition (1Log) observed at 4mg/ml. Herpes simplex virus-1 and Porcine Parvovirus were mildly inhibited, whereas no antiviral activity was observed with respect to Adenovirus-5, Human Herpesvirus-6, Porcine Reproductive and Respiratory Syndrome Virus. No HA virucidal activity was ever observed against any of the viruses tested. Kinetic experiments showed that both Coxsackievirus B5 and Herpes simplex virus-1 replication were consistently inhibited, not influenced by the time of HA addition, during the virus replication cycle.CONCLUSIONS: the spectrum of the antiviral activity exhibited by HA against both RNA and DNA viruses, known to have different structures (with or without envelope) and replication strategies, suggests a non specific mechanism of action, probably involving cell membrane-virus interaction steps. The results of the kinetic experiments support this hypothesis

Citrullination: the loss of tolerance and development of autoimmunity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and pannus formation, which can lead to severe destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Moreover the presence of autoantibodies to citrullinated proteins in sera of patients with RA enhances the strength of this hypothesis. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as phosphorylation, glycosylation and citrullination can increase the morphological and the functional diversity of the proteome

A New Early Predictor of Fatal Outcome for COVID-19 in an Italian Emergency Department: The Modified Quick-SOFA

Background: Since 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a rapidly spreading pandemic. The present study aims to compare a modified quick SOFA (MqSOFA) score with the NEWS-2 score to predict in-hospital mortality (IHM), 30-days mortality and recovery setting. Methods: All patients admitted from March to October 2020 to the Emergency Department of St. Anna Hospital, Ferrara, Italy with clinically suspected SARS-CoV-2 infection were retrospectively included in this single-centre study and evaluated with the MqSOFA and NEWS-2 scores. Statistical and logistic regression analyses were applied to our database. Results: A total of 3359 individual records were retrieved. Among them, 2716 patients were excluded because of a negative nasopharyngeal swab and 206 for lacking data; thus, 437 patients were eligible. The data showed that the MqSOFA and NEWS-2 scores equally predicted IHM (p < 0.001) and 30-days mortality (p < 0.001). Higher incidences of coronary artery disease, congestive heart failure, cerebrovascular accidents, dementia, chronic kidney disease and cancer were found in the deceased vs. survived group. Conclusions: In this study we confirmed that the MqSOFA score was non-inferior to the NEWS-2 score in predicting IHM and 30-days mortality. Furthermore, the MqSOFA score was easier to use than NEWS-2 and is more suitable for emergency settings. Neither the NEWS-2 nor the MqSOFA scores were able to predict the recovery setting

Dysregulation of NF–Y splicing drives metabolic rewiring and aggressiveness in colon cancer

NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing, NF-YAl and NF-YAs, which differ in the transactivation domain. Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer (CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patients’ survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by the worst prognosis. Through the analysis of 3D cellular models, we demonstrated that altered expression of genes related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl in metabolic flexibility of cancer cells that adjust their metabolism in response to environmental changes to potentiate migration. The zebrafish xenograft model confirmed the metastatic potential triggered by NF-YAl in CRC cells. Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination

Consistency conditions and trace anomalies in six dimensions

Conformally invariant quantum field theories develop trace anomalies when defined on curved backgrounds. We study again the problem of identifying all possible trace anomalies in d=6 by studying the consistency conditions to derive their 10 independent solutions. It is known that only 4 of these solutions represent true anomalies, classified as one type A anomaly, given by the topological Euler density, and three type B anomalies, made up by three independent Weyl invariants. However, we also present the explicit expressions of the remaining 6 trivial anomalies, namely those that can be obtained by the Weyl variation of local functionals. The knowledge of the latter is in general necessary to disentangle the universal coefficients of the type A and B anomalies from calculations performed on concrete models.Comment: 16 pages, LaTe

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches

Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cyto-kine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the re-lapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell im-pairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunother-apeutic approaches in these settings

Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00–0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00–0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02–0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics

Early palliative care versus usual haematological care in multiple myeloma: retrospective cohort study

Objectives Although early palliative care (EPC) is beneficial in acute myeloid leukaemia, little is known about EPC value in multiple myeloma (MM). We compared quality indicators for palliative and end of life (EOL) care in patients with MM receiving EPC with those of patients who received usual haematological care (UHC).Methods This observational, retrospective study was based on 290 consecutive patients with MM. The following indicators were abstracted: providing psychological support, assessing/managing pain, discussing goals of care, promoting advance care plan, accessing home care services; no anti MM treatment within 14 and 30 days and hospice length of stay >7 days before death; no cardiopulmonary resuscitation, no intubation, <2 hospitalisations and emergency department visits within 30 days before death. Comparisons were performed using unadjusted and confounder adjusted regression models.Results 55 patients received EPC and 231 UHC. Compared with UHC patients, EPC patients had a significantly higher number of quality indicators of care (mean 2.62 +/- 1.25 vs 1.12 +/- 0.95; p<0.0001)); a significant reduction of pain intensity over time (p<0.01) and a trend towards reduced aggressiveness at EOL, with the same survival (5.3 vs 5.46 years; p=0.74)).Conclusions Our data support the value of integrating EPC into MM routine practice and lay the groundwork for future prospective comparative studies