ASFV epitope mapping by high density peptides microarrays.

African swine fever (ASF) is an acute, highly contagious and deadly infectious disease. It is a threat to animal health with major potential economic and societal impact. Despite decades of ASF vaccine research, still some gaps in knowledge are hindering the development of a functional vaccine. Worth mentioning are gaps in understanding the mechanism of ASF infection and immunity, as well as the fact that - in case of this disease - virus proteins, so-called protective antigens, responsible for inducing protective immune responses in pigs are not identified yet. In this paper we elaborate on a methodology to identify protective antigens based on epitope mapping by microarray technology. High density peptide microarrays, combined with fluorescence scanning, have been used to analyze the interaction of peptide sequences of African swine fever virus (ASFV) proteins with antibodies present in inactivated serum from infected and healthy animals. The study evidenced ASFV proteins already under the radar for vaccine development, such as p54, and identified specific sequences in those proteins that may become the focus for future vaccine candidates. Such methodology is amenable to automation and high-throughput and may help developing better targeting for next generation vaccines.

Differences in Physico-Chemical Properties and Immunological Response in Nanosimilar Complex Drugs: The Case of Liposomal Doxorubicin.

This study aims to highlight the impact of physicochemical properties on the behaviour of nanopharmaceuticals and how much carrier structure and physiochemical characteristics weigh on the effects of a formulation. For this purpose, two commercially available nanosimilar formulations of Doxil and their respective carriers were compared as a case study. Although the two formulations were "similar", we detected different toxicological effects (profiles) in terms of in vitro toxicity and immunological responses at the level of cytokines release and complement activation (iC3b fragment), that could be correlated with the differences in the physicochemical properties of the formulations. Shedding light on nanosimilar key quality attributes of liposome-based materials and the need for an accurate characterization, including investigation of the immunological effects, is of fundamental importance considering their great potential as delivery system for drugs, genes, or vaccines and the growing market demand.

Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays.

Introduction: The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity tests challenging. In the present study, we have analysed to what extent fluctuations of the complement system of different individuals will have an impact on the standardisation of immunological tests. Methods: We treated commercially available pooled sera (PS) from healthy males, individual sera from healthy donors and from patients suffering from cancer, immunodeficiency and allergies with small molecules and liposomes. Changes of iC3b protein levels measured in enzyme-linked immunosorbent assays served as biomarker for complement activation. Results: The level of complement activation in PS differed significantly from responses of individual donors (p < 0.01). Only seven out of 32 investigated sera from healthy donors responded similarly to the pooled serum. This variability was even more remarkable when investigating the effect of liposomes on the complement activation in sera from donors with pre-existing pathologies. Neither the 26 sera of donors with allergies nor sera of 16 donors with immunodeficiency responded similar to the PS of healthy donors. Allergy sufferers showed an increase in iC3b levels of 4.16-fold changes when compared to PS treated with liposomes. Discussion: Our studies demonstrate that the use of pooled serum can lead to an over- or under-estimation of immunological response in particular for individuals with pre-existing pathologies. This is of high relevance when developing medical products based on nanomaterials and asks for a review of the current practice to use PS from healthy donors for the prediction of immunological effects of drugs in patients. A better understanding of individual toxicological responses to xenobiotics should be an essential part in safety assessments.

Round Robin into Best Practices for the Determination of Indentation Size Effects.

The paper presents a statistical study of nanoindentation results obtained in seven European laboratories which have joined a round robin exercise to assess methods for the evaluation of indentation size effects. The study focuses on the characterization of ferritic/martensitic steels T91 and Eurofer97, envisaged as structural materials for nuclear fission and fusion applications, respectively. Depth-controlled single cycle measurements at various final indentation depths, force-controlled single cycle and force-controlled progressive multi-cycle measurements using Berkovich indenters at room temperature have been combined to calculate the indentation hardness and the elastic modulus as a function of depth applying the Oliver and Pharr method. Intra- and inter-laboratory variabilities have been evaluated. Elastic modulus corrections have been applied to the hardness data to compensate for materials related systematic errors, like pile-up behaviour, which is not accounted for by the Oliver and Pharr theory, and other sources of instrumental or methodological bias. The correction modifies the statistical hardness profiles and allows determining more reliable indentation size effects.

Depth-Sensing Hardness Measurements to Probe Hardening Behaviour and Dynamic Strain Ageing Effects of Iron during Tensile Pre-Deformation.

This work reports results from quasi-static nanoindentation measurements of iron, in the un-strained state and subjected to 15% tensile pre-straining at room temperature, 125 °C and 300 °C, in order to extract room temperature hardness and elastic modulus as a function of indentation depth. The material is found to exhibit increased disposition for pile-up formation due to the pre-straining, affecting the evaluation of the mechanical properties of the material. Nanoindentation data obtained with and without pre-straining are compared with bulk tensile properties derived from the tensile pre-straining tests at various temperatures. A significant mismatch between the hardness of the material and the tensile test results is observed and attributed to increased pile-up behaviour of the material after pre-straining, as evidenced by atomic force microscopy. The observations can be quantitatively reconciled by an elastic modulus correction applied to the nanoindentation data, and the remaining discrepancies explained by taking into account that strain hardening behaviour and nano-hardness results are closely affected by dynamic strain ageing caused by carbon interstitial impurities, which is clearly manifested at the intermediate temperature of 125 °C.

A Microfluidic Human Model of Blood-Brain Barrier Employing Primary Human Astrocytes.

The neurovascular unit (NVU) is the most important biological barrier between vascular districts and central nervous system (CNS) parenchyma, which maintains brain homeostasis, protects the CNS from pathogens penetration, and mediates neuroimmune communication. T lymphocytes migration across the blood-brain barrier is heavily affected in different brain diseases, representing a major target for novel drug development. In vitro models of NVU could represent a primary tool to investigate the molecular events occurring at this interface. To move toward the establishment of personalized therapies, a patient-related NVU-model is set, incorporating human primary astrocytes integrated into a microfluidic platform. The model is morphologically and functionally characterized, proving to be an advantageous tool to investigate human T lymphocytes transmigration and thus the efficacy of potential novel drugs affecting this process.

[Do our elderly people suffer malnutrition? An evaluation of their nutritional state]. / Están nuestros ancianos desnutridos? Valoración del estado nutricional.

Elderly are particulary prone to suffer nutritional disbalance, mainly desnutrition. This alterations carry physical and functional consequences. For this reason, the scheduled evaluation of nutritional status must take part in the elderly nursing care. The evaluation must be performed in a individual basis, depending on the health and functional status. A description of screening test for healthy people are included, as is a functional health patterns, paying special attention to the dietary record and some anthropometric testing, to finalize with laboratory tests in the more complex patients.

[Cachexia]. / Caquexia. Paciente terminal de cáncer.

Cachexia is a frequent syndrome in patients suffering from advanced cancer; it is characterized by anorexia, weight loss, and malnutrition, which combined with other psychic and social consequences lead to a deterioration in a patient's quality of life. Various factors play a role in the development of cachexia; these depend on the patient, the type of tumor, and the treatments received. Its complexity warrant the intervention of an interdisciplinary team, in which nursing plays an essential role. Up to present time, the results of pharmaceutical treatment have been rather unfavorable; therefore, nutritional treatments based on advise for concrete problems and dietary supplements gain importance; enteral or parenteral nutrition are reserved for selected cases. Other important aspects are psychological support, control of associated symptoms and the prevention and treatment of any complication which may appear.