Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure

Aims Left ventricular (LV) mass increase is considered part of composite target organ damage in hypertension and an independent risk factor for cardiovascular (CV) events. This study was designed to explore whether left ventricular mass index (LVMI) is associated with cognitive decline and dementia in elderly subjects, independently of blood pressure (BP) levels. Methods and results Four hundred subjects (mean age 79 ± 6 years) were studied. Left ventricular mass was measured echocardiographically in accordance with American Society of Echocardiography and normalized for body height to the 2.7 (LVMI). Global cognitive function was evaluated with the mini-mental state examination (MMSE) (maximum score 30). Dementia was defined as an MMSE score <21. Arterial stiffness was evaluated as carotid–femoral pulse wave velocity by Complior®. Prevalence of hypertension was 70% and diabetes mellitus was diagnosed in 25%. No significant differences in traditional CV risk factors were observed across LVMI quartiles. Mini-mental state examination showed an inverse trend across LVMI quartiles (the higher the LVMI, the lower the MMSE, P for trend <0.05); systolic and diastolic BP levels were not different across LVMI quartiles. In multivariable logistic regression models, including age, sex, BP levels, and use of antihypertensive drugs as covariates, the highest LVMI was found to be independently associated with a two-fold higher likelihood of having dementia. The association persisted significant even after adjustment for arterial stiffness. Conclusion In elderly subjects, LVMI is associated with a progressive cognitive decline. This association is independent of BP levels and/or large artery stiffness

COVID-19 and arrhythmia: The factors associated and the role of myocardial electrical impulse propagation. An observational study based on cardiac telemetric monitoring

BACKGROUND: The heart is commonly involved in COVID-19, and rhythm disorders have been largely reported. OBJECTIVE: To evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19. METHODS: Each patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias). RESULTS: Two-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07–1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38–68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003–1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20–302.51); p = 0.0004]. CONCLUSION: Arrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading)

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneu-monia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of &gt;7 and &gt;328 U/L, respectively

Impact of chronic liver disease upon admission on COVID-19 in-hospital mortality: Findings from COVOCA study

Background Italy has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory. Objectives Aim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy). Methods COVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission. Results Among 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42–4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39–14.46; p&lt;0.001) and malignancies (OR 2.62, 95%CI 1.21–5.68; p = 0.015) disclosed an independent association with a poor prognosis, Glasgow Coma Scale (GCS) and Respiratory Severity Scale allowed to identify at higher mortality risk. Sensitivity analysis further enhanced these findings. Conclusion Mortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage

Disordered protein-graphene oxide co-assembly and supramolecular biofabrication of functional fluidic devices

Supramolecular chemistry offers an exciting opportunity to assemble materials with molecular precision. However, there remains an unmet need to turn molecular self-assembly into functional materials and devices. Harnessing the inherent properties of both disordered proteins and graphene oxide (GO), we report a disordered protein-GO co-assembling system that through a diffusion-reaction process and disorder-to-order transitions generates hierarchically organized materials that exhibit high stability and access to non-equilibrium on demand. We use experimental approaches and molecular dynamics simulations to describe the underlying molecular mechanism of formation and establish key rules for its design and regulation. Through rapid prototyping techniques, we demonstrate the system's capacity to be controlled with spatio-temporal precision into well-defined capillary-like fluidic microstructures with a high level of biocompatibility and, importantly, the capacity to withstand flow. Our study presents an innovative approach to transform rational supramolecular design into functional engineering with potential widespread use in microfluidic systems and organ-on-a-chip platforms

Relationship between Antibody Susceptibility and Lipopolysaccharide O-Antigen Characteristics of Invasive and Gastrointestinal Nontyphoidal Salmonellae Isolates from Kenya

Background: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal. Methodology/Principal findings: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p\u3c0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features. Conclusion/Significance: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level

Orally Administered P22 Phage Tailspike Protein Reduces Salmonella Colonization in Chickens: Prospects of a Novel Therapy against Bacterial Infections

One of the major causes of morbidity and mortality in man and economically important animals is bacterial infections of the gastrointestinal (GI) tract. The emergence of difficult-to-treat infections, primarily caused by antibiotic resistant bacteria, demands for alternatives to antibiotic therapy. Currently, one of the emerging therapeutic alternatives is the use of lytic bacteriophages. In an effort to exploit the target specificity and therapeutic potential of bacteriophages, we examined the utility of bacteriophage tailspike proteins (Tsps). Among the best-characterized Tsps is that from the Podoviridae P22 bacteriophage, which recognizes the lipopolysaccharides of Salmonella enterica serovar Typhimurium. In this study, we utilized a truncated, functionally equivalent version of the P22 tailspike protein, P22sTsp, as a prototype to demonstrate the therapeutic potential of Tsps in the GI tract of chickens. Bacterial agglutination assays showed that P22sTsp was capable of agglutinating S. Typhimurium at levels similar to antibodies and incubating the Tsp with chicken GI fluids showed no proteolytic activity against the Tsp. Testing P22sTsp against the three major GI proteases showed that P22sTsp was resistant to trypsin and partially to chymotrypsin, but sensitive to pepsin. However, in formulated form for oral administration, P22sTsp was resistant to all three proteases. When administered orally to chickens, P22sTsp significantly reduced Salmonella colonization in the gut and its further penetration into internal organs. In in vitro assays, P22sTsp effectively retarded Salmonella motility, a factor implicated in bacterial colonization and invasion, suggesting that the in vivo decolonization ability of P22sTsp may, at least in part, be due to its ability to interfere with motility… Our findings show promise in terms of opening novel Tsp-based oral therapeutic approaches against bacterial infections in production animals and potentially in humans

International migration and the rise of the ‘civil’ nation

This is an Accepted Manuscript of an article published in Journal of Ethnic and Migration Studies on 2 March 2016, available online: http://www.tandfonline.com/10.1080/1369183X.2016.1155980Scholars largely agree that immigration policies in Western Europe have switched to a liberal, civic model. Labelled as ‘civic turn’, ‘civic integration’ or ‘liberal convergence’, this model is not identically applied across countries, since national institutions, traditions and identifications still matter. Even so, the main focus is on processes which allow or prevent migrants to be incorporated into nations usually taken for granted in their meanings. Moving from policies to discourses, this article aims to interrogate what kind of nation is behind these policies as a way to further scrutinise the ‘civic turn’. Exploring how the term ‘civility’ and its adjectivisations are discursively deployed in Italian parliamentary debates on immigration and integration issues, the article points to two opposite narratives of nation. While one mobilises civility in order to rewrite the nation in terms of a common, inclusive, civic ‘we’, the other uses civility to reaffirm the conflation between national identity and the identity of the ethno-cultural majority. These findings suggest the importance of exploring the ‘civic turn’ not only across countries, but also across political parties within the same country to capture the ways in which a liberal, civic convergence in political discourses might hide divergent national boundary mechanisms

Efficacy and durability of multifactorial intervention on mortality and MACEs:a randomized clinical trial in type-2 diabetic kidney disease

Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT0053592

Tales of the City: Outsiders' Descriptions of Cities in the Early Modern Period

Ambassadors, merchants, bankers, scholars, artists, architects, to name but a few, were all groups that travelled extensively during the Early Modern period. The outsiders’ gaze on the cities they came into contact with- perceived both in terms of architectural space and social practices- were frequently communicated formally or informally by means of letters, dispatches and other literary means. Within an international perspective, the recipients of such information- whether friends, family or princely employers- were hungry for details of daily life and new fashions, as well as for reports of construction projects or urban developments. Such descriptive texts offer a complimentary point of view to that of sources such as chronicles and diaries, tax accounts and legislation, that were produced by insider-residents, and that are widely used by scholars of urban history. This volume seeks to bring together papers that consider such outsiders’ descriptions of the cities they came into contact with. Papers cross national or linguistic boundaries, with the observer immersed in environments quite alien to their own, pointing out what did outsiders particularly notice, to what degree was their point of view conditioned by such factors as their own urban experience, or that of their guide or guide-book, how far is the content of descriptions shaped by their audience