Gestational age and hospital utilization : three-years follow-up of an area-based birth cohort

OBJECTIVE: To investigate differences by gestational age in emergency department visits and re-hospitalizations during the three years following childbirth discharge. METHODS: We performed a historical cohort study in Lazio Region, Italy, for infants born in 2007-2008 to resident mothers. Health administrative data were used. Analysis was performed by multinomial logistic regression. RESULTS: Of 90 545 infants, more than 50% had at least one emergency department visit, and 18.8% at least one re-hospitalization. After the exclusion of infants with congenital anomalies, relative risk ratios of re-hospitalization and, to a lesser extent, of emergency department visits increased by decreasing gestational age; the two events were also higher for mothers ≤35 years of age, with low education and of Italian nationality. Residency outside the metropolitan area was associated with an increased risk of re-hospitalization and a decreased risk of emergency department visits. CONCLUSION: During the three years following childbirth discharge, re-hospitalizations and, to a lesser extent, emergency department use are inversely related to gestational age at birth; socio-demographic factors have an effect on the risk of infant use of hospital resources independent of gestational age

Resilience and Vulnerability of Historical Centers: the Case of the District of Camerino in the Marche Region

The seismic events that hit central Italy in 2016, causing extensive damage to cultural heritage and the loss of entire villages, showed the extreme fragility of the Marche territorial system with strong repercussions on the economic and social development. In the historic villages, the high inherent seismic vulnerability of the building makes it difficult to apply regulations oriented to the protection and preservation of historical and cultural values: strategies for the recovery of the buildings seem very complex. The historical building is generally characterized by a high building density, a scarcity of urban voids and an articulated accessibility system. In recent years the Marche region has developed, due to the intensification of earthquakes, a particular susceptibility to seismic risk. The historic centres have shown a scarce capability to adaptation and difficulties in hypothesizing new scenarios after the damage. In this context, we want to define an analytical method of the systemic vulnerability in the historical centres; this vulnerability is considered as a result of the complex interaction of individual structural units, aggregates and urban spaces. The aim is to compare this vulnerability with the effects that the earthquake really had on the buildings: the knowledge of the real behaviour in the historic centres will guide the research towards the definition of actions aimed at the mitigation of the seismic risk through the reduction of intrinsic vulnerabilities in the building and the implementation of the capability to face the earthquake, in order to develop a “new resilience”. The district of Camerino is taken as a case study; it’s a territorial hub of services and activities as well as being one of the largest inhabited centres affected by the 2016-2017 earthquake

Quantitative analysis of the thermal distortions in a 100 W CW Nd:YAG ceramic slab laser.

Making use of an interferometric diagnostic system, we analyze the thermo-mechanical distortions taking place in the slab shaped ceramic Nd:YAG active medium of a 100 W class laser. These distortions are collected in different pumping regimes, both in static situations and during transient warm-up, and compared to the results of computer simulations. This procedure enables us to determine the relevance of different stress causes and thus to increase the specific power extraction of the active slab module

Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy

Background In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection.Methods This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose.Findings 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p < 0.001); the protective role of antibodies was preserved over the whole follow up (HR=0.57, 95%CI=0.43-0.75, p < 0.001), with a significant reduction (HR=1.40, 95%CI=1.01-1.94, p=0.04) for the Omicron cases. The third dose significantly reduced the risk of infection (HR=0.44, 95%CI=0.21-0.90,p=0.025) during the Omicron wave.Interpretation The risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/

Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells

Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

Master regulator protein p53, popularly known as the “guardian of genome” is the hub for regulation of diverse cellular pathways. Depending on the cell type and severity of DNA damage, p53 protein mediates cell cycle arrest or apoptosis, besides activating DNA repair, which is apparently achieved by regulation of its target genes, as well as direct interaction with other proteins. p53 is known to repress target genes via multiple mechanisms one of which is via recruitment of chromatin remodelling Sin3/HDAC1/2 complex. Sin3 proteins (Sin3A and Sin3B) regulate gene expression at the chromatin-level by serving as an anchor onto which the core Sin3/HDAC complex is assembled. The Sin3/HDAC co-repressor complex can be recruited by a large number of DNA-binding transcription factors. Sin3A has been closely linked to p53 while Sin3B is considered to be a close associate of E2Fs. The theme of this study was to establish the role of Sin3B in p53-mediated gene repression. We demonstrate a direct protein-protein interaction between human p53 and Sin3B (hSin3B). Amino acids 1–399 of hSin3B protein are involved in its interaction with N-terminal region (amino acids 1–108) of p53. Genotoxic stress induced by Adriamycin treatment increases the levels of hSin3B that is recruited to the promoters of p53-target genes (HSPA8, MAD1 and CRYZ). More importantly recruitment of hSin3B and repression of the three p53-target promoters upon Adriamycin treatment were observed only in p53+/+ cell lines. Additionally an increased tri-methylation of the H3K9 residue at the promoters of HSPA8 and CRYZ was also observed following Adriamycin treatment. The present study highlights for the first time the essential role of Sin3B as an important associate of p53 in mediating the cellular responses to stress and in the transcriptional repression of genes encoding for heat shock proteins or proteins involved in regulation of cell cycle and apoptosis

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background and purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3–100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3–50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff