Biological risk in Italian prisons: data analysis from the second to the fourth wave of COVID-19 pandemic

BackgroundThe management of COVID-19 in Italian prisons triggered considerable concern at the beginning of the pandemic due to numerous riots which resulted in inmate deaths, damages and prison breaks. The aim of this study is to shed some light, through analysis of the infection and relevant disease parameters, on the period spanning from the second to the fourth wave of the outbreak in Italy's prisons. MethodsReproductive number (Rt) and Hospitalisation were calculated through a Eulerian approach applied to differential equations derived from compartmental models. Comparison between trends was performed through paired t-test and linear regression analyses. ResultsThe infection trends (prevalence and Rt) show a high correlation between the prison population and the external community. Both the indices appear to be lagging 1 week in prison. The prisoners' Rt values are not statistically different from those of the general population. The hospitalisation trend of inmates strongly correlates with the external population's, with a delay of 2 weeks. The magnitude of hospitalisations in prison is less than in the external community for the period analysed. ConclusionsThe comparison with the external community revealed that in prison the infection prevalence was greater, although Rt values showed no significant difference, and the hospitalisation rate was lower. These results suggest that the consistent monitoring of inmates results in a higher infection prevalence while a wide vaccination campaign leads to a lower hospitalisation rate. All three indices demonstrate a lag of 1 or 2 weeks in prison. This delay could represent a useful time-window to strengthen planned countermeasures

From Heterogeneous Sensor Networks to Integrated Software Services: Design and Implementation of a Semantic Architecture for the Internet of Things at ARCES@UNIBO

The Internet of Things (IoTs) is growing fast both in terms of number of devices connected and of complexity of deployments and applications. Several research studies an- alyzing the economical impact of the IoT worldwide identify the interoperability as one of the main boosting factor for its growth, thanks to the possibility to unlock novel commercial opportunities derived from the integration of heterogeneous systems which are currently not interconnected. However, at present, interoperability constitutes a relevant practical issue on any IoT deployments that is composed of sensor platforms mapped on different wireless technologies, network protocols or data formats. The paper addresses such issue, and investigates how to achieve effective data interoperability and data reuse on complex IoT deployments, where multiple users/applications need to consume sensor data produced by heterogeneous sensor networks. We propose a generic three-tier IoT architecture, which decouples the sensor data producers from the sensor data consumers, thanks to the intermediation of a semantic broker which is in charge of translating the sensor data into a shared ontology, and of providing publish-subscribe facilities to the producers/consumers. Then, we describe the real-world implementation of such architecture devised at the Advanced Research Center on Electronic System (ARCES) of the University of Bologna. The actual system collects the data produced by three different sensor networks, integrates them through a SPARQL Event Processing Architecture (SEPA), and supports two front- end applications for the data access, i.e. a web dashboard and an Amazon Alexa voice service

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

On the Potential of Relational Databases for the Detection of Clusters of Infection and Antibiotic Resistance Patterns

In recent years, several bacterial strains have acquired significant antibiotic resistance and can, therefore, become difficult to contain. To counteract such trends, relational databases can be a powerful tool for supporting the decision-making process. The case of Klebsiella pneumoniae diffusion in a central region of Italy was analyzed as a case study. A specific relational database is shown to provide very detailed and timely information about the spatial–temporal diffusion of the contagion, together with a clear assessment of the multidrug resistance of the strains. The analysis is particularized for both internal and external patients. Tools such as the one proposed can, therefore, be considered important elements in the identification of infection hotspots, a key ingredient of any strategy to reduce the diffusion of an infectious disease at the community level and in hospitals. These types of tools are also very valuable in the decision-making process related to antibiotic prescription and to the management of stockpiles. The application of this processing technology to viral diseases such as COVID-19 is under investigation

Evaluation of circ_100219 and miR-135b in serum and exosomes of healthy pregnant women

Aim: Circular RNAs (circRNAs) are recently discovered and highly stable noncoding RNAs acting as gene regulators. These circRNAs can function as miRNA sponges, thereby upregulating or downregulating miRNA target gene expression. MiR-135b is expressed in placenta tissue and can be found in maternal circulation, thus playing a functional role in pregnancy. This miR is a target of circ_100219. This preliminary study was aimed to evaluate circ_100219 and miR-135b expression in pregnant and nonpregnant women, and explore the relationship between circ_100219 and miR-135b in serum and exosomes.Methods: Total RNA was isolated from serum and exosomes of 30 healthy pregnant women (32.9\u2009\ub1\u20095.1 years) between 23-27 gestational weeks and 30 healthy nonpregnant women (31.3\u2009\ub1\u20095.4 years). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_100219 and miR-135b expression. GAPDH and U6 snRNA were chosen as reference for normalizing expression levels. The differences between pregnant and nonpregnant women were assessed with Mann-Whitney test and correlation with Spearman's test.Results: The circ_100219 expression levels were significantly lower both in serum and exosomes of second trimester pregnant women compared to the control group (p\u2009<\u2009.0001), whilst Mir-135b expression levels were significantly higher in pregnant than in the control group (p\u2009<\u2009.0001). A significant negative correlation was observed between circ_100219 and miR-135b expression levels in both serum and exosomes (r\u2009=\u2009-0.34 and p\u2009=\u2009.009; r\u2009=\u2009-0.31 and p\u2009=\u2009.01, respectively). The circ_100219:miR-135b ratio was significantly increased in nonpregnant women compared to the pregnant group, in both serum and exosomes (49.0 versus 1.1, p\u2009<\u2009.0001 and 2042.4 versus 28.5, p\u2009<\u2009.0001, respectively).Conclusions: Our results confirm a role for circ_100219 and miR-135b in physiological pregnancy. Further studies are needed to investigate the circ_100219:miR-135b ratio in pregnancy complications