Overcoming health challenges:a journey through horizon scanning, disinfection, and biocatalytic functionalization strategies

Our society confronts a multitude of health challenges, ranging from non-communicable diseases like heart disease, cancer, and diabetes to persistent communicable diseases and emerging pandemics. These challenges necessitate comprehensive strategies for prevention, treatment, and public health intervention. The studies outlined in this thesis connect to these pressing concerns.Horizon Scanning was presented as a valuable tool for monitoring potential societal health issues and innovations in the medical field. In collaboration with EMA, WHO, and EC-JRC, 25 signals of trends and technologies were identified and discussed. These signals of change reflect the multifaceted nature of global innovation, spurred by events such as the COVID-19 pandemic, which accelerated the implementation of information technologies in the medical domain and pushed forward platform technologies, redefining medicinal products and personalized healthcare. While these innovations hold promise for patients, they require careful regulatory implementation.A recurring problem highlighted from the study and that necessitates a multifaceted approach is AMR. In this context, the thesis also focuses on the importance of disinfection in curbing pathogen transmission. The effectiveness of a portable UV-C device in disinfecting complex objects, was measured through an ad-hoc biological assessment strategy. The results suggest the potential for broader applications in object disinfection. Additionally the thesis delves into the potential of enzymatic functionalization to modify nanoparticles, such as viruses and carbon nanotubes, for improving their applicability in biomedicine. The proposed biocatalytic approach provides flexibility in modifications, holding promises for the incorporation of various properties

Health horizons: Future trends and technologies from the European Medicines Agency’s horizon scanning collaborations

In medicines development, the progress in science and technology is accelerating. Awareness of these developments and their associated challenges and opportunities is essential for medicines regulators and others to translate them into benefits for society. In this context, the European Medicines Agency uses horizon scanning to shine a light on early signals of relevant innovation and technological trends with impact on medicinal products. This article provides the results of systematic horizon scanning exercises conducted by the Agency, in collaboration with the World Health Organization (WHO) and the European Commission’s Joint Research Centre’s (DG JRC). These collaborative exercises aim to inform policy-makers of new trends and increase preparedness in responding to them. A subset of 25 technological trends, divided into three clusters were selected and reviewed from the perspective of medicines regulators. For each of these trends, the expected impact and challenges for their adoption are discussed, along with recommendations for developers, regulators and policy makers

Compton-thick AGN in the NuSTAR era III: A systematic study of the torus covering factor

We present the analysis of a sample of 35 candidate Compton thick (CT-) active galactic nuclei (AGNs) selected in the nearby Universe (average redshift ~0.03) with the Swift-BAT 100-month survey. All sources have available NuSTAR data, thus allowing us to constrain with unprecedented quality important spectral parameters such as the obscuring torus line-of-sight column density (N_{H, z}), the average torus column density (N_{H, tor}) and the torus covering factor (f_c). We compare the best-fit results obtained with the widely used MyTorus (Murphy et al. 2009) model with those of the recently published borus02 model (Balokovic et al. 2018) used in the same geometrical configuration of MyTorus (i.e., with f_c=0.5). We find a remarkable agreement between the two, although with increasing dispersion in N_{H, z} moving towards higher column densities. We then use borus02 to measure f_c. High-f_c sources have, on average, smaller offset between N_{H, z} and N_{H, tor} than low-f_c ones. Therefore, low f_c values can be linked to a "patchy torus" scenario, where the AGN is seen through an over-dense region in the torus, while high-f_c objects are more likely to be obscured by a more uniform gas distribution. Finally, we find potential evidence of an inverse trend between f_c and the AGN 2-10 keV luminosity, i.e., sources with higher f_c values have on average lower luminosities.Comment: 35 Pages, 23 Figures. Accepted for publication in Ap

Environmental assessment of antimicrobial coatings for packaged fresh milk

Antimicrobial coatings are being increasingly used as a means to extend the shelf life of food products. This extension helps consumers cut down on the food waste generated at household level, while at the same time reducing the impact, which these products' life cycle has on the environment. The aim of this Life Cycle Assessment study is thus to assess the consequences on the environment arising from the application of an antimicrobial coating onto the packaging of a fresh milk product, while also taking into account the reduction in milk waste. The antimicrobial coating considered is a synthetic derivative of lauric acid. The application of the coating involves additional environmental impacts caused by all the inputs and outputs which occur during its life cycle. At the same time, however, the use of this coating allows to extend the fresh milk's shelf life with a consequent reduction in food waste. The data related to the production and application of the coating were provided by the packaging laboratory of the Institute of Agrochemistry and Food Technology (Valencia) and by manufacturing companies. The data related to food waste, milk processing, refrigeration transports, storage, and end of life of both product and packaging were obtained from previous studies, institutional reports and Ecoinvent database v2.2. The Midpoint Impact 2002 method was used to assess impacts. The results show how the reduction in milk waste achievable by using the coating generates higher environmental benefits than the impacts caused by the coating's life cycle due to milk saving. Furthermore this study demonstrates the importance of including food waste in Life Cycle Assessment studies of packaging systems. The connection between packaging design and food waste is a decisive aspect in the evaluation of actual environmental sustainability and should thus be considered in all assessments of packaging solutions. (C) 2015 Elsevier Ltd. All rights reserved.Manfredi, M.; Fantin, V.; Vignali, G.; Gavara Clemente, R. (2015). Environmental assessment of antimicrobial coatings for packaged fresh milk. Journal of Cleaner Production. 95:291-300. doi:10.1016/j.jclepro.2015.02.0482913009

An Efficient UV-C Disinfection Approach and Biological Assessment Strategy for Microphones

Featured Application Disinfection of microphones by using UV-C to be applied in the entertainment industry to prevent infections as a consequence of microphone sharing between individuals. Hygiene is a basic necessity to prevent infections, and though it is regarded as vital in general, its importance has been stressed again during the pandemic. Microbes may spread through touch and aerosols and thereby find their way from host to host. Cleaning and disinfection of possibly contaminated surfaces prevents microbial spread, thus reducing potential illnesses. One item that is used by several people in a way that promotes close contact by touch and aerosol formation is the microphone. A microphone is a complex piece of equipment with respect to shape and various materials used to fabricate it and, hence, its disinfection is challenging. A new device has been developed to efficiently sterilize microphones by using UV-C and a biological assessment has been done to identify its efficacy and translatability. For this investigation, a contamination procedure was developed by using M13 bacteriophage as a model to illustrate the effectiveness of the disinfection. The susceptibility to UV-C irradiation of M13 in solution was compared to that of the PR8 H1N1 influenza virus, which has a similar UV-C susceptibility as SARS-CoV-2. It was found that 10 min of UV-C treatment reduced the percentage of infectious M13 by 99.3% based on whole microphone inoculation and disinfection. UV-C susceptibility of M13 and influenza in suspension were found to be very similar, indicating that the microphone sterilization method and device function are highly useful and broadly applicable

Testing the blast-wave AGN feedback scenario in MCG-03-58-007

We report the first Atacama large millimeter/submillimeter array observations of MCG-03-58-007, a local ($z=0.03236\pm0.00002$, this work) AGN ($L_{AGN}\sim10^{45}~\rm erg~s^{-1}$), hosting a powerful X-ray ultra-fast ($v=0.1c$) outflow (UFO). The CO(1-0) line emission is observed across $\sim18\,$kpc scales with a resolution of $\sim 1\,\rm kpc$. About 78\% of the CO(1-0) luminosity traces a galaxy-size rotating disk. However, after subtracting the emission due to such rotating disk, we detect with a S/N=20 a residual emission in the central $\sim 4\,$kpc. Such residuals may trace a low velocity ($v_{LOS}=170\,\rm km\,s^{-1}$) outflow. We compare the momentum rate and kinetic power of such putative molecular outflow with that of the X-ray UFO and find $\dot{P}_{out}/\dot{P}_{UFO}=0.3\pm0.2$ and $\dot{E}_{mol}/\dot{E}_{UFO}\sim4\cdot10^{-3}$. This result is at odds with the energy-conserving scenario suggested by the large momentum boosts measured in some other molecular outflows. An alternative interpretation of the residual CO emission would be a compact rotating structure, distinct from the main disk, which would be a factor of $\sim10-100$ more extended and massive than typical circumnuclear disks revealed in Seyferts. However, in both scenarios, our results rule out the hypothesis of a momentum-boosted molecular outflow in this AGN, despite the presence of a powerful X-ray UFO. [Abridged]Comment: Accepted for publication in MNRAS. 13 pages, 11 figure

Unveiling Sub-pc Supermassive Black Hole Binary Candidates in Active Galactic Nuclei

The elusive supermassive black hole binaries (SMBHBs) are thought to be the penultimate stage of galaxy mergers, preceding a final coalescence phase. SMBHBs are sources of continuous gravitational waves, possibly detectable by pulsar timing arrays; the identification of candidates could help in performing targeted gravitational wave searches. Due to SMBHBs’ origin in the innermost parts of active galactic nuclei (AGN), X-rays are a promising tool for unveiling their presence, by means of either double Fe Kα emission lines or periodicity in their light curve. Here we report on a new method for selecting SMBHBs by means of the presence of a periodic signal in their Swift Burst Alert Telescope (BAT) 105 month light curves. Our technique is based on Fisher’s exact g-test and takes into account the possible presence of colored noise. Among the 553 AGN selected for our investigation, only the Seyfert 1.5 galaxy Mrk 915 emerges as a candidate SMBHB; from subsequent analysis of its light curve we find a period P0 = 35 ± 2 months, and the null hypothesis is rejected at the 3.7σ confidence level. We also present a detailed analysis of the BAT light curve of the only previously X-ray-selected binary candidate source in the literature, the Seyfert 2 galaxy MCG+11-11-032. We find P0 = 26.3 ± 0.6 months, consistent with the one inferred from previously reported double Fe Kα emission lines

Providing a nurse-led complex nursing INtervention FOcused on quality of life assessment on advanced cancer patients: The INFO-QoL pilot trial.

PURPOSE Unmet needs for advanced-disease cancer patients are fatigue, pain, and emotional support. Little information is available about the feasibility of interventions focused on patient-reported outcome measurement developed according to the Medical Research Council (MRC) Framework in advanced-disease cancer patients. We aimed to pilot a nurse-led complex intervention focused on QoL assessment in advanced-disease cancer patients. METHODS The INFO-QoL study was based on an exploratory, nonequivalent comparison group, pre-test-post-test design. Study sites received either the INFO-QoL intervention or usual care. Adult advanced-disease cancer patients admitted to hospice inpatient units that gave their informed consent were included in the study. Subjects were 187 patients and their families and 19 healthcare professionals. We evaluated feasibility, acceptability, and patients' outcomes using the Integrated Palliative Care Outcome Scale. RESULTS Nineteen healthcare professionals were included. The mean competence score increased significantly over time (p < 0.001) and the mean usefulness score was high 8.63 (±1.36). In the post-test phase, 54 patients were allocated to the experimental unit and 36 in the comparison unit. Compared to the comparison unit, in the experimental unit anxiety (R2 = 0.07; 95% CI = -0.06; 0.19), family anxiety (R2 = 0.22; 95% CI = -0.03; 0.41), depression (R2 = 0.31; 95% CI = -0.05; 0.56) and sharing feelings (R2 = 0.09; 95% CI = -0.05; 0.23), were improved between pre-test and post-test phase. CONCLUSIONS The INFO-QoL was feasible and potentially improved psychological outcomes. Despite the high attrition rate, the INFO-QoL improved the quality and safety culture for patients in palliative care settings

Tunable Chemokine Production by Antigen Presenting Dendritic Cells in Response to Changes in Regulatory T Cell Frequency in Mouse Reactive Lymph Nodes

BACKGROUND: Although evidence exists that regulatory T cells (Tregs) can suppress the effector phase of immune responses, it is clear that their major role is in suppressing T cell priming in secondary lymphoid organs. Recent experiments using two photon laser microscopy indicate that dendritic cells (DCs) are central to Treg cell function and that the in vivo mechanisms of T cell regulation are more complex than those described in vitro. PRINCIPAL FINDINGS: Here we have sought to determine whether and how modulation of Treg numbers modifies the lymph node (LN) microenvironment. We found that pro-inflammatory chemokines -- CCL2 (MCP-1) and CCL3 (MIP-la) -- are secreted in the LN early (24 h) after T cell activation, that this secretion is dependent on antigen-specific DC-T cell interactions, and that it was inversely related to the frequency of Tregs specific for the same antigen. Furthermore, we demonstrate that Tregs modify the chemoattractant properties of antigen-presenting DCs, which, as the frequency of Tregs increases, fail to produce CCL2 and CCL3 and to attract antigen-specific T cells. CONCLUSIONS: These results substantiate a major role of Tregs in LN patterning during antigen-specific immune responses