Place attachment and place identity amongst older Italians in Newcastle Upon Tyne

PhD ThesisIn the social gerontology literature, there is a wide agreement on the importance of affective bonds with places for a positive experience of ‘ageing-in-place’. This includes a sense of attachment to and identification with places, also defined as a ‘sense of home’. However, the ways in which these affective bonds with places are negotiated by ageing migrants is yet a fairly neglected area of research. Nevertheless, with increasing numbers of older migrants adopting a transnational lifestyle or returning to the country of origin after retirement, there is a pertinent need to explore ageing migrants’ meanings of the affective bonds with places. Through an ethnographic approach, this project aims to gain a better understanding of the sense of attachment to and identification with places by members of an older Italian migrant population in Newcastle upon Tyne, UK. The main argument of this work is that a ‘sense of home’ – or a lack of it –shapes the conditions for ageing-in-place in the context of migration. Firstly, I explore how the negotiation of belonging, which relates to social and political aspects of the environment, contributes to a ‘sense of home’ in the context of migration. Secondly, I illustrate how the attachment to places left pre-migration, through transnationality and ‘home-making’ practices, elucidates the expectation of ageing. Thirdly, I address how the facilitators to a ‘sense of home’ in the context of migration mark a new status in later life. Finally, I focus on the barriers to a sense of identification with the places inhabited, that co-exist with a sense of attachment, but that undermine the sense of belonging to these. Ultimately, challenging the assumption of older Italian migrants as a homogeneous population, this work highlights how the diversity within the group is shaped by the relationship established with places in later life.Newcastle Biomedical Research Centre and MyPlace (Mobility and Place for an Age-Friendly Environment, EPSRC) for funding my stud

Cardiac Troponin T capture and detection in real-time via epitope-imprinted polymer and optical biosensing

Millions of premature deaths per year from cardiovascular diseases represent a global threat urging governments to increase global initiatives, as advised by World Health Organization. In particular, together with prevention and management of risk factors, the development of portable platforms for early diagnosis of cardiovascular disorders appears a fundamental task to carry out. Contemporary assays demonstrated very good accuracy for diagnosis of acute myocardial infarction (AMI), but they are based on expensive and fragile capture antibodies. Accordingly, also considering the massive demand from developing countries, we have devoted our study to an affinity-based biosensor for detection of troponin T (TnT), a preferred biomarker of AMI. This combines a stable and inexpensive molecularly imprinted polymer (MIP) based on polydopamine (PDA) with surface plasmon resonance (SPR) transduction. Herein we report the fast and specific answer upon TnT binding onto an epitope- imprinted surface that strongly encourages the further development toward antibody-free point-of-care testing for cardiac injury

Colorimetric determination of p-nitrophenol by using ELISA microwells modified with an adhesive polydopamine nanofilm containing catalytically active gold nanoparticles

A microplate method is described for the quantification of p-nitrophenol (p-NPh) in urine samples where it can be found after exposure to certain insecticides such as methyl parathion or paraoxon. The assay is based on the use of a polydopamine (PDA) film doped with gold nanoparticles (AuNPs). The latter exerts a catalytic effect on the reduction of nitrophenols by NaBH4. PDA has adhesive properties and can be used to fix the AuNPs on several solid substrates, here ELISA polystyrene microwells. The optical and catalytic properties of different populations of AuNPs spontaneously grown on PDA films were investigated, mainly in terms of the relationship between AuNPs@PDA nanocomposite preparation and its catalytic activity and stability. The reduction of o-, m-, and p-nitrophenols by NaBH4 in aqueous solution was exploited as model study. The approach demonstrates that useful kinetic information on the catalytic effect can be obtained on 96-wells simultaneously by a conventional ELISA reader at a fixed wavelength of 415 nm. The method was successfully applied to the quantification of p-NPh in (spiked) urine samples and gave high reproducibility (RSD = 3.5%) and a 6.30 μM (836 μg/L) detection limit. [Figure not available: see fulltext.]. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature

A LysLysLys-tag as trigger in polynorepinephrine epitope imprinting: The case study of soluble PD-L1 detection in serum by optical-based sensing

Polycatecholamines (pCAs)-based molecularly imprinted polymers (MIPs) represent the new performing generation of biocompatible ligand/receptor mimetics. In this context, dealing with MIPs synthesis for bio-macromolecules detection/extraction, one of the critical steps in ensuring effective binding affinity for the parent molecule is the selection of suitable epitopes for pCAs imprinting. To address this challenge, here we investigated the ability of lysine (K) residues to trigger the epitope imprinting process into a polynorepinephrine (PNE) matrix. To this aim, we first designed a set of model epitopes composed of three K and six alanine (A) residues to investigate the influence of each 'KA' combination on the imprinting process and the resulting binding performance by Surface Plasmon Resonance (SPR). Only the case of three flanking K residues in N-terminus arose as an excellent trigger for epitope imprinting. The efficacy of the 3K-tag strategy was then evaluated on two peptide templates belonging to soluble programmed cell death protein 1 ligand (PD-L1), which is of great interest as a cancer biomarker in liquid biopsies. These templates were selected due to their negligible natural ability to be imprinted into the PNE matrix and were modified with 3K-tags, in N-, C-, and N/C- positions, respectively. The SPR sensor developed by exploiting the N-3K tag strategy allowed us to achieve excellent sensitivity (0.31 ± 0.04 ng mL-1) and repeatability (avCV% = 4.5) in human serum samples. This strategy opens new insights both for epitopes' design for pCAs-based mimetics and as triggering tags when native epitopes display negligible imprinting capabilities

Real-time tau protein detection by sandwich-based piezoelectric biosensing: Exploring tubulin as a mass enhancer

Human tau protein is one of the most advanced and accepted biomarkers for AD and tauopathies diagnosis in general. In this work, a quartz crystal balance (QCM) immunosensor was developed for the detection of human tau protein in buffer and artificial cerebrospinal fluid (aCSF), through both direct and sandwich assays. Starting from a conventional immuno-based sandwich strategy, two monoclonal antibodies recognizing different epitopes of tau protein were used, achieving a detection limit for the direct assay in nanomolar range both in HBES-EP and aCSF. Afterward, for exploring alternative specific receptors as secondary recognition elements for tau protein biosensing, we tested tubulin and compared its behavior to a conventional secondary antibody in the sandwich assay. Tau–tubulin binding has shown an extended working range coupled to a signal improvement in comparison with the conventional secondary antibody-based approach, showing a dose–response trend at lower tau concentration than is usually investigated and closer to the physiological levels in the reference matrix for protein tau biomarker. Our results open up new and encouraging perspectives for the use of tubulin as an alternative receptor for tau protein with interesting features due to the possibility of taking advantage of its polymerization and reversible binding to this key hallmark of Alzheimer’s disease

Colorimetric determination of total protein content in serum based on the polydopamine/protein adsorption competition on microplates

We report a facile, low-cost and safe analytical method for estimation of total protein content, even in complex matrix like human serum, by exploiting the competition between proteins and polydopamine (PDA) for surface binding. The surface coating has been examined by using a microplate reader taking the advantage of the PDA absorbance in the visible region, obtaining new insights into the modelling of polydopamine deposition and polymer/protein adsorption competition. This is helpful for rational development of imprinted biosensors, and potentially offering a with broad applications ranging from diagnostic tools in medicine to food analysis. The isothermal adsorption of polydopamine on polystyrene surface of multi-well plate displays a Langmuir-shaped curve. It allows the determination of the parameters of polymer film formation useful for any analytical assay depending on the surface coating. Among these, the molecular imprinting and the optical and acoustic evanescent sensing

Structurally Constrained MUC1-Tn Mimetic Antigen as Template for Molecularly Imprinted Polymers (MIPs): A Promising Tool for Cancer Diagnostics

Abnormal glycoconjugates have distinctly been recognized as potential biomarkers for cancer diagnosis. A great deal of attention has been focused on Tn antigen, an oversimplified mucin-1 O-glycan, over-expressed in different cancers. Herein, we investigate the possibility to replace the use of anti-Tn monoclonal antibodies with an innovative class of catecholamine-based Molecularly Imprinted Polymers (MIPs), emerging in recent years as promising tools for bioanalytical applications. MIPs are synthetic receptors characterized by high sensitivity and specificity towards the imprinted target. Here, original polynorepinephrine-based MIPs coupled to Surface Plasmon Resonance biosensing for Tn antigen recognition are reported. We have verified the imprinting and binding capacity of these MIPs towards very small antigenic entities, represented by the natural Tn antigen and the TnThr mimetic 1 (conjugated to BSA or linked to a MUC1 hexapeptide analogue), and compared the biosensor performances with an anti-Tn monoclonal antibody. The results clearly display the effectiveness of the pursued imprinting strategies

Biweekly Hizentra® in Primary Immunodeficiency: a Multicenter, Observational Cohort Study (IBIS)

Immunoglobulin G (IgG) replacement therapy is a standard treatment for patients with primary immunodeficiency diseases (PIDs). Hizentra®, a 20% human subcutaneous IgG (SCIG), is approved for biweekly administration for PIDs. The aim of the multicenter IBIS study was to prospectively investigate the efficacy of biweekly Hizentra® compared with previous IVIG or SCIG treatment regimens in patients with PIDs. The study consisted of a 12-month retrospective period followed by 12-month prospective observational period. The main endpoints included pre-infusion IgG concentrations, proportion of patients with serious bacterial infections (SBIs), other infections, hospitalizations due to PID-related illnesses, and days with antibiotics during the study periods. Of the 36 patients enrolled in the study, 35 patients continued the study (mean age 26.1 ± 14.4 years; 68.6% male). The mean pre-infusion IgG levels for prior immunoglobulin regimens during the retrospective period (7.84 ± 2.09 g/L) and the prospective period (8.55 ± 1.76 g/L) did not show any significant variations (p = 0.4964). The mean annual rate of SBIs/patient was 0.063 ± 0.246 for both prospective and retrospective periods. No hospitalizations related to PIDs were reported during the prospective period versus one in the retrospective period. All patients were either very (76.5%) or quite (23.5%) satisfied with biweekly Hizentra® at the end of the study. In conclusion, the IBIS study provided real-world evidence on the efficacy of biweekly Hizentra® in patients with PIDs, thus verifying the data generated by the pharmacometric modeling and simulation study in a normal clinical setting

Disability assessment using Google Maps

Objectives To evaluate the concordance between Google Maps  application (GM ) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). Materials and methods This is a cross-sectional multicenter study. AS and EDSS were calculated using GM  and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. Results Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM  and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1–7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01–1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04–1.17, p = 0.002) were associated with discrepancies between GM  and routine clinical scoring. Conclusion GM  could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM  should be considered for validation in further clinical studies