Defining the latent phase of labour: is it important?

Background and rationale. The latent phase of labour is recognised as a period of uncertainty for women and midwives. There is evidence from the literature of considerable variation in labour definitions and practice. Stimulated by discussion at an international maternity research conference, the authors set out to explore opinions regarding the need for labour-stage definitions.  Aim. To identify health professionals’ views on the need for a definition of the onset and the end of the latent phase of labour.  Methods. This was an opportunistic, semi-structured, online survey of attendees at a maternity care research conference, which included midwives, other clinicians, academics, advocates and user representatives. Attendees (approximately 100) were invited to participate through a single email invitation sent by the conference committee and containing a link to the survey. Consent was sought on the landing page. Ethical approval was obtained from Bournemouth University’s research ethics committee. Quantitative questions were analysed using simple descriptive statistics using IBM SPSS Statistics Version 24. Open questions were analysed using content analysis and where participants gave a more detailed answer, these were analysed using a thematic approach.  Findings. Participants in the survey (n=21) came from 12 countries. Most of the participants thought that there was a need to define the onset of the latent phase (n=15, 71%). Common characteristics were cited, but the main theme in the open comments referred to the importance of women’s perceptions of labour onset. Most participants (n = 18, 86%) thought that there was a need to define the end of the latent phase. This was felt necessary because current practice within facilities is usually dictated by a definition. The characteristics suggested were also not unexpected and there was some consensus; but the degree of cervical dilatation that signified the end of the latent phase varied among participants. There was significant debate about whether a prolonged latent phase was important; for example, was it associated with adverse consequences. Most participants thought it was important (n=15, 71%), but comments indicated that the reasons for this were complex. Themes included the value that women attached to knowing the duration of labour and the need to support women in the latent phase.  Implications for practice. The findings from this small, opportunistic survey reflect the current debate within the maternal health community regarding the latent phase of labour. There is a need for more clarity around latent phase labour (in terms of both the definition and the support offered) if midwives are to provide care that is both woman centred and evidence-based. The findings will inform the development of a larger survey to explore attitudes towards labour definitions

The Effects of Ca²⁺ Concentration and E200K Mutation on the Aggregation Propensity of PrP^C: A Computational Study

<div><p>The propensity of cellular prion protein to aggregation is reputed essential for the initiation of the amyloid cascade that ultimately lead to the accumulation of neurotoxic aggregates. In this paper, we extended and applied an already reported computational workflow [Proteins 2015; 83: 1751–1765] to elucidate in details the aggregation propensity of PrP protein systems including wild type, wild type treated at different [Ca²⁺] and E200K mutant. The application of the computational procedure to two segments of PrP^C, i.e. 125–228 and 120–231, allowed to emphasize how the inclusion of complete C-terminus and last portion (120–126) of the neurotoxic segment 106–126 may be crucial to unveil significant and unexpected interaction properties. Indeed, the anchoring of N-terminus on H2 domain detected in the wild type resulted to be disrupted upon either E200K mutation or Ca²⁺ binding, and to unbury hydrophobic spots on the PrP^C surface. A peculiar dinuclear Ca²⁺ binding motif formed by the C-terminus and the S2-H2 loop was detected for [Ca²⁺] > 5 mM and showed similarities with binding motifs retraced in other protein systems, thus suggesting a possible functional meaning for its formation. Therefore, we potentiated the computational procedure by including a tool that clusterize the minima of molecular interaction fields of a proteinand delimit the regions of space with higher hydrophobic or higher hydrophilic character, hence, more likely involved in the self-assembly process. Plausible models for the self-assembly of either the E200K mutated or Ca²⁺-bound PrP^C were sketched and discussed. The present investigation provides for structure-based information and new prompts that may represent a starting point for future experimental or computational works on the PrP^C aggregation.</p></div

Comparison of PrP primary structures.

<p>Segment a (125–228,top), segment b (120–231, middle), and whole 90–231 segment(down) of the human prion protein. * indicates amide capping by acetyl or N-methyl amide of N or C terminal, respectively. The neurotoxic peptide segment 106–126 is underlined.</p

Averaged MEP isosurfaces.

<p>Reported PrP were Ib (left), IIb (middle), and Vb (right) subsets. Positive and negative isosurfaces are depicted as blue and red meshes, respectively. Qualitative insight of the charge amount per region is also reported.</p

Atomic fluctuations of PrP backbone.

<p>Root mean squared fluctuations per residue (rmsf) for I (circle), II (square), and V (triangle) systems and II-I (bold, square) and V-I (bold, triangle) rmsf difference per residue (Δrmsf); a and b systems reported on top and bottom, respectively. Boxes highlight the residues with Δrmsf values outside the range of −0.05–0.05 nm (dashed lines).</p

Summary of the investigated PrP systems and their labels.

<p>Summary of the investigated PrP systems and their labels.</p

Simplified scheme of the formation of PrP aggregates.

<p>Simplified scheme of the formation of PrP aggregates.</p

Hypothesized structures of E200K-PrP^C aggregates.

<p>(A) Representation of the E200K-PrP^C with its clusters of DRY (yellow) and HOH (red) minima. (B) Two E200K mutants chained through region 1-region 3 interactions. (C) Interaction of two E200K tetramers by the approach of hydrophobic clusters on region 2.</p

The Ca²⁺-coordinating sites on the PrP structure.

<p>(A) Distribution of Ca²⁺ coordination sites by the superposition of all III-V systems. Details of the dinuclear coordination motif detected in region 1 obtained by (B) molecular dynamics simulation and (C) quantum mechanical optimization of a reduced model retrieved from system Vb.</p

Computational workflow for the estimation of the interaction properties of a protein system.

<p>Computational workflow for the estimation of the interaction properties of a protein system.</p