278 research outputs found

    Probing degeneracy in antigen-antibody recognition at the immunodominant site of foot-and-mouth disease virus

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    Antigen-antibody binding is regarded as one of the most representative examples of specific molecular recognition in nature. The simplistic view of antigenic recognition in terms of a lock-and-key mechanism is obsolete, as it is evident that both antigens and antibodies are flexible and can undergo substantial mutual adaptation. This flexibility is the source of complexities such as degeneracy and nonadditivity in antigenic recognition. We have used surface plasmon resonance to study the effects of combining multiple amino acid replacements within the sequence of the antigenic GH loop of foot-and-mouth disease virus, Our aim was 2-fold: to explore the extent to which antigenic degeneracy can be extended in this particular case, and to search for potential nonadditive effects in introducing multiple amino acid replacements. Combined Spain analysis of one such multiply substituted peptide by SPR, solution NMR and X-ray diffraction shows that antigenic degeneracy can be expected as long as residues directly interacting with the paratope are conserved and the peptide bioactive folding is unaltered

    Intravenous fluid therapy for hospitalized and critically ill children: rationale, available drugs and possible side effects

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    Human beings are constituted mainly of water. In particular, children's total body water might reach 75-80% of their body weight, compared to 60-70% in adults. It is therefore not surprising, that children, especially hospitalized newborns and infants, are markedly prone to water and electrolyte imbalances. Parenteral fluid therapy is a cornerstone of medical treatment and is thus of exceptional relevance in this patient population. It is crucial to appreciate the fact that intravenous fluids are drugs with very different characteristics, different indications, contraindications and relevant side effects. In the present review, we will summarize the physiology and pathophysiology of water and electrolyte balance, underlining the importance and high prevalence of non-osmotic antidiuretic hormone release in hospitalized and critically ill children. Furthermore, we will discuss the characteristics and potential side effects of available crystalloids for the paediatric population, making a clear distinction between fluids that are hypotonic or isotonic as compared to normal plasma. Finally, we will review the current clinical practice regarding the use of different parenteral fluids in children, outlining both the current consensus on fluids employed for resuscitation and replacement and the ongoing debate concerning parenteral maintenance fluids

    Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy

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    In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship

    Identifying sources of strength: resilience from the perspective of older people receiving long-term community care

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    This study seeks to explore the sources of strength giving rise to resilience among older people. Twenty-nine in-depth interviews were conducted with older people who receive long-term community care. The interviews were subjected to a thematic content analysis. The findings suggest that the main sources of strength identified among older people were constituted on three domains of analysis; the individual-, interactional and contextual domain. The individual domain refers to the qualities within older people and comprises of three sub-domains, namely beliefs about one’s competence, efforts to exert control and the capacity to analyse and understand ones situation. Within these subdomains a variety of sources of strength were found like pride about ones personality, acceptance and openness about ones vulnerability, the anticipation on future losses, mastery by practising skills, the acceptance of help and support, having a balanced vision on life, not adapting the role of a victim and carpe-diem. The interactional domain is defined as the way older people cooperate and interact with others to achieve their personal goals. Sources of strength on this domain were empowering (in)formal relationships and the power of giving. Lastly, the contextual domain refers to a broader political-societal level and includes sources of strength like the accessibility of care, the availability of material resources and social policy. The three domains were found to be inherently linked to each other. The results can be used for the development of positive, proactive interventions aimed at helping older people build on the positive aspects of their lives
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