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Escherichia coli O157:H7 has become a global public health and a food safety problem. Despite the implementation of control strategies that guarantee the safety in various products, outbreaks persist and new alternatives are necessary to reduce this pathogen along the food chain. Recently, our group isolated and characterised lytic bacteriophages against E. coli O157:H7 with potential to be used as biocontrol agents in food. To this end, phages need certain requirements to allow their manufacture and application. The aim of this study was to determine the physical stability and allergenic potential of free and microencapsulated (ME) bacteriophage cocktails against E. coli O157:H7. In vitro and in vivo studies were performed to determine phage survival under different pH, gastrointestinal conditions, temperature and UV light intensities. Results showed that the stability of ME phages was significantly (P<0.05) higher than free phages after ultraviolet irradiation, pH conditions between 3 to 7, and exposure to temperatures between at -80°C and 70°C. Both formulations were highly sensitive to very low pH in simulated gastric fluid, but stable in bile salts. In vivo studies in mice confirmed these phages passed through the gastrointestinal tract and were excreted in faeces. In silico, full-length alignment analysis showed that all phage proteins were negative for allergenic potential, but different predicting criteria classified seven phage proteins with a very low probability to be an allergen. In conclusion, these data demonstrated that microencapsulation provided a greater stability to phage formulation under stress conditions and assure a more suitable commercial formulation for the biological control of E. coli O157:H7.

The New World (NW) mammarenavirus group includes several zoonotic highly pathogenic viruses, such as Junin (JUNV) or Machupo (MACV). Contrary to the Old World mammarenavirus group, these viruses are not able to completely suppress the innate immune response and trigger a robust interferon (IFN)-I response via retinoic acid-inducible gene I (RIG-I). Nevertheless, pathogenic NW mammarenaviruses trigger a weaker IFN response than their nonpathogenic relatives do. RIG-I activation leads to upregulation of a plethora of IFN-stimulated genes (ISGs), which exert a characteristic antiviral effect either as lone effectors, or resulting from the combination with other ISGs or cellular factors. The dsRNA sensor protein kinase receptor (PKR) is an ISG that plays a pivotal role in the control of the mammarenavirus infection. In addition to its well-known protein synthesis inhibition, PKR further modulates the overall IFN-I response against different viruses, including mammarenaviruses. For this study, we employed Tacaribe virus (TCRV), the closest relative of the human pathogenic JUNV. Our findings indicate that PKR does not only increase IFN-I expression against TCRV infection, but also affects the kinetic expression and the extent of induction of Mx1 and ISG15 at both levels, mRNA and protein expression. Moreover, TCRV fails to suppress the effect of activated PKR, resulting in the inhibition of a viral titer. Here, we provide original evidence of the specific immunomodulatory role of PKR over selected ISGs, altering the dynamic of the innate immune response course against TCRV. The mechanisms for innate immune evasion are key for the emergence and adaptation of human pathogenic arenaviruses, and highly pathogenic mammarenaviruses, such as JUNV or MACV, trigger a weaker IFN response than nonpathogenic mammarenaviruses. Within the innate immune response context, PKR plays an important role in sensing and restricting the infection of TCRV virus. Although the mechanism of PKR for protein synthesis inhibition is well described, its immunomodulatory role is less understood. Our present findings further characterize the innate immune response in the absence of PKR, unveiling the role of PKR in defining the ISG profile after viral infection. Moreover, TCRV fails to suppress activated PKR, resulting in viral progeny production inhibition.

The zoonotic Old World mammarenavirus Lassa (LASV) causes severe hemorrhagic fever with high mortality and morbidity in humans in endemic regions. The development of effective strategies to combat LASV infections is of high priority, given the lack of a licensed vaccine and restriction on available treatment to off-label use of ribavirin. A better understanding of the fundamental aspects of the virus’s life cycle would help to improve the development of novel therapeutic approaches. Host cell entry and restriction factors represent major barriers for emerging viruses and are promising targets for therapeutic intervention. In addition to the LASV main receptor, the extracellular matrix molecule dystroglycan (DG), the phosphatidylserine-binding receptors of the Tyro3/Axl/Mer (TAM), and T cell immunoglobulin and mucin receptor (TIM) families are potential alternative receptors of LASV infection. Therefore, the relative contributions of candidate receptors to LASV entry into a particular human cell type are a complex function of receptor expression and functional DG availability. Here, we describe the role of two receptor tyrosine kinases (RTKs), Axl and hepatocyte growth factor receptor (HGFR), in the presence and absence of glycosylated DG for LASV entry. We found that both RTKs participated in the macropinocytosis-related LASV entry and, regardless of the presence or absence of functional DG, their inhibition resulted in a significant antiviral effect.

Purpose With the aim of monitoring the existing regulations that are applicable to community of owners facing delinquency, in view of the importance of this issue for the achievement of the Urban Agenda, the present study aims to analyse the most stringent and controversial measures available for the community of owners facing delinquency from a comparative perspective. Design/methodology/approach The present work addresses the recent legislative amendments that have taken place at national level in this field in several countries and analyses to what extent they have addressed the delinquency problem faced by community of owners. Findings The current paper shows that, in the end, legal certainty, the prospective legal and economic effects on mortgage lending and constitutional concerns are the underlying reasons behind the reluctance to implement some stringent measures to face delinquency. It also shows that recent amendments concerning alternative dispute resolution mechanisms are a missed opportunity. Social implications Community of owners plays a key role in cities for the achievement of the Urban Agenda, so the periodical contributions from co-owners are paramount to the proper implementation of urban regeneration, energy efficiency and accessibility policies. To this end, the paper analyses existing regulations that are applicable to community of owners facing delinquency, which may increase in the coming years due to the current socioeconomic context. Originality/value This paper builds on existing research and goes one step further by addressing the recent legislative amendments that have taken place recently at national level in this field. These measures may serve as an inspiration to other EU legal systems.

Purpose This paper aims to explain the provisions of the New Directive on Secondary Mortgage Markets, in particular it considers consumers protection issues and whether the principles of Life Time Contracts epitomise the proper balancing of principles underlying European law, now set out in the EU Charter of Fundamental Rights. Design/methodology/approach The present work outlines first the legacy of the European financial and mortgage crisis and the need for new rules on cross-border sales of non-performing loans (NPLs). Then it provides an overview of the Directive, analyses the complexity of the cross-border supervision and addresses consumer protection issues and the potential role the Life Time Contracts and the EU Charter of Fundamental Rights may play to protect consumers in this field. Findings The current paper shows that the provisions of the Directive, the Mortgage Credit Directive and the Consumer Credit Directive fail to protect consumer borrowers when NPLs are sold to third parties. Advancing this human rights protection could transcend the regulatory, legislative and consumer protection approaches of the Union in this area. Social implications The Directive establishes the regulatory and operational structures for the sale of NPLs. However, some important issues have been raised, including how the cross-border supervision will operate to protect consumers. Accordingly, the research may help to increase consumer protection in this field. Originality/value This paper explains the provisions of the New Directive on Secondary Mortgage Markets and its complex and unique cross-border regulatory framework, as yet untested. This work may serve as an inspiration for the EU to improve existing consumer rules at the EU level.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19). Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.

Experimental and field observations evidence the effects of capillarity in narrow pores on inhibiting the thermodynamic stability of gas hydrates and controlling their saturation. Thus, precise estimates of the gas hydrate global inventory require models that accurately describe gas hydrate stability in sediments. Here, an equilibrium model for hydrate formation in sediments that accounts for capillary inhibition effects is developed and validated against experimental data. Analogous to water freezing in pores, the model assumes that hydrate formation is controlled by the sediment pore size distribution and the balance of capillary forces at the hydrate–liquid interface. To build the formulation, we first derive the Clausius–Clapeyron equation for the thermodynamic equilibrium of methane and water chemical potentials. Then, this equation is combined with the van Genuchten’s capillary pressure to relate the thermodynamic properties of the system to the sediment pore size distribution and hydrate saturation. The model examines the influence of the sediment pore size distribution on hydrate saturation through the simulation of hydrate formation in sand, silt, and clays, under equilibrium conditions and without mass transfer limitations. The results show that at pressure–temperature conditions typically found in the seabed, capillary effects in very fine-grained clays can limit the maximum hydrate saturation below 20% of the host sediment porosity.

Friedreich’s ataxia (FRDA) is a comparatively rare autosomal recessive neurological disorder primarily caused by the homozygous expansion of a GAA trinucleotide repeat in intron 1 of the FXN gene. The repeat expansion causes gene silencing that results in deficiency of the frataxin protein leading to mitochondrial dysfunction, oxidative stress and cell death. The GAA repeat tract in some cases may be impure with sequence variations called interruptions. It has previously been observed that large interruptions of the GAA repeat tract, determined by abnormal MboII digestion, are very rare. Here we have used triplet repeat primed PCR (TP PCR) assays to identify small interruptions at the 5′ and 3′ ends of the GAA repeat tract through alterations in the electropherogram trace signal. We found that contrary to large interruptions, small interruptions are more common, with 3′ interruptions being most frequent. Based on detection of interruptions by TP PCR assay, the patient cohort (n = 101) was stratified into four groups: 5′ interruption, 3′ interruption, both 5′ and 3′ interruptions or lacking interruption. Those patients with 3′ interruptions were associated with shorter GAA1 repeat tracts and later ages at disease onset. The age at disease onset was modelled by a group-specific exponential decay model. Based on this modelling, a 3′ interruption is predicted to delay disease onset by approximately 9 years relative to those lacking 5′ and 3′ interruptions. This highlights the key role of interruptions at the 3′ end of the GAA repeat tract in modulating the disease phenotype and its impact on prognosis for the patient.

The current context of uncertainty regarding the long-term future of pensions in European countries due to the lack of public resources, coupled with the unstoppable aging of the population, may force the elderly to use private financial instruments so as to meet their needs. One of them is the reverse mortgage, which enables them to withdraw equity from their homes without being required to pay back the loan during their lifetime. The truth, however, is that its use is not widespread, generally speaking, in European countries. This paper explores the regulation of the reverse mortgage in Spain and Italy, countries which have a legal framework for equity release schemes, and taking into account the legislation other countries have enacted to regulate this financial instrument (so the experiences in Ireland, the United Kingdom and the United States are taken into consideration), it concludes by formulating recommendations for policy makers to promote the marketing of this financial instrument.

Disabilities of the lower extremities significantly affect a person’s ability to perform activities of daily living. Many people have been affected by this type of disability due to birth disease or injury from accidents, strokes or even old age. The technical aids used in this type of disability are very basic, and rehabilitation is mainly performed by therapists. Rehabilitation consists of repetitions of exercises with normal movements that must be performed for prolonged periods of time. On the other hand, therapists, having to support the weight of the patient, tend to get injured. This paper introduces the design and modeling a robotic device intended to assist the therapist in the rehabilitation of sit-to-stand (STS) and walking movements, focusing primarily on the technical aspects of the system. The robot is designed to safely support the user’s weight and guide the user with appropriate movements according to the usual biomechanics of STS. This paper presents the solution of the inverse kinematic modeling of both the position and velocity of the robot mechanism, as well as the dynamic analysis. A series of simulations is conducted to evaluate the performance of the proposed mechanical architecture during the STS task, providing quantitative information on the system dynamics and the interaction forces between the user and the robot. The mathematical model was employed in the design of a prototype intended for children aged 8–12 years, capable of supporting up to 50 kg and providing a vertical motion range of 20–90 cm. The main structural elements of the robot, its control architecture, and its operation during the execution of the STS task are described. Finally, the conclusions of this work are discussed, and future work derived from this research is outlined.