Analysis of platelet-rich plasma extraction variations in platelet and blood components between 4 common commercial kits

Background: Platelet-rich plasma (PRP) has been extensively used as a treatment in tissue healing in tendinopathy, muscle injury, and osteoarthritis. However, there is variation in methods of extraction, and this produces different types of PRP. Purpose: To determine the composition of PRP obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-study comparisons. Study Design: Controlled laboratory study. Methods: Three normal adults each donated 181 mL of whole blood, some of which served as a control and the remainder of which was processed through 4 PRP separation kits: GPS III (Biomet Biologics), Smart-Prep2 (Harvest Terumo), Magellan (Arteriocyte Medical Systems), and ACP (Device Technologies). The resultant PRP was tested for platelet count, red blood cell count, and white blood cell count, including differential in a commercial pathology laboratory. Glucose and pH measurements were obtained from a blood gas autoanalyzer machine. Results: Three kits taking samples from the “buffy coat layer” were found to have greater concentrations of platelets (3-6 times baseline), while 1 kit taking samples from plasma was found to have platelet concentrations of only 1.5 times baseline. The same 3 kits produced an increased concentration of white blood cells (3-6 times baseline); these consisted of neutrophils, leukocytes, and monocytes. This represents high concentrations of platelets and white blood cells. A small drop in pH was thought to relate to the citrate used in the sample preparation. Interestingly, an unexpected increase in glucose concentrations, with 3 to 6 times greater than baseline levels, was found in all samples. Conclusion:This study reveals the variation of blood components, including platelets, red blood cells, leukocytes, pH, and glucose in PRP extractions. The high concentrations of cells are important, as the white blood cell count in PRP samples has frequently been ignored, being considered insignificant. The lack of standardization of PRP preparation for clinical use has contributed at least in part to the varying clinical efficacy in PRP use. Clinical Relevance: The variation of platelet and other blood component concentrations between commercial PRP kits may affect clinical treatment outcomes. There is a need for standardization of PRP for clinical use

Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis

One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates

Triangulating molecular evidence to prioritize candidate causal genes at established atopic dermatitis loci

Genome-wide association studies for atopic dermatitis (AD) have identified 25 reproducible loci. We attempt to prioritize candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for AD aetiology, including expression, protein and DNA methylation QTL datasets in skin or immune-relevant tissues which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction, and features such as promoter-enhancer interactions, expression studies and variant fine-mapping. For each gene at each locus, we condensed the evidence into a prioritization score. Across the investigated loci, we detected significant enrichment of genes with adaptive immune regulatory function and epidermal barrier formation among the top prioritized genes. At 8 loci, we were able to prioritize a single candidate gene (IL6R, ADO, PRR5L, IL7R, ETS1, INPP5D, MDM1, TRAF3). In addition, at 6 of the 25 loci, our analysis prioritizes less familiar candidates (SLC22A5, IL2RA, MDM1, DEXI, ADO, STMN3). Our analysis provides support for previously implicated genes at several AD GWAS loci, as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery

The vertebrate phylotypic stage and an early bilaterian-related stage in mouse embryogenesis defined by genomic information

BACKGROUND: Embryos of taxonomically different vertebrates are thought to pass through a stage in which they resemble one another morphologically. This "vertebrate phylotypic stage" may represent the basic vertebrate body plan that was established in the common ancestor of vertebrates. However, much controversy remains about when the phylotypic stage appears, and whether it even exists. To overcome the limitations of studies based on morphological comparison, we explored a comprehensive quantitative method for defining the constrained stage using expressed sequence tag (EST) data, gene ontologies (GO), and available genomes of various animals. If strong developmental constraints occur during the phylotypic stage of vertebrate embryos, then genes conserved among vertebrates would be highly expressed at this stage. RESULTS: We established a novel method for evaluating the ancestral nature of mouse embryonic stages that does not depend on comparative morphology. The numerical "ancestor index" revealed that the mouse indeed has a highly conserved embryonic period at embryonic day 8.0–8.5, the time of appearance of the pharyngeal arch and somites. During this period, the mouse prominently expresses GO-determined developmental genes shared among vertebrates. Similar analyses revealed the existence of a bilaterian-related period, during which GO-determined developmental genes shared among bilaterians are markedly expressed at the cleavage-to-gastrulation period. The genes associated with the phylotypic stage identified by our method are essential in embryogenesis. CONCLUSION: Our results demonstrate that the mid-embryonic stage of the mouse is indeed highly constrained, supporting the existence of the phylotypic stage. Furthermore, this candidate stage is preceded by a putative bilaterian ancestor-related period. These results not only support the developmental hourglass model, but also highlight the hierarchical aspect of embryogenesis proposed by von Baer. Identification of conserved stages and tissues by this method in various animals would be a powerful tool to examine the phylotypic stage hypothesis, and to understand which kinds of developmental events and gene sets are evolutionarily constrained and how they limit the possible variations of animal basic body plans

Building better Sex Robots: Lessons from Feminist Pornography

How should we react to the development of sexbot technology? Taking their cue from anti-porn feminism, several academic critics lament the development of sexbot technology, arguing that it objectifies and subordinates women, is likely to promote misogynistic attitudes toward sex, and may need to be banned or restricted. In this chapter I argue for an alternative response. Taking my cue from the sex positive ‘feminist porn’ movement, I argue that the best response to the development of ‘bad’ sexbots is to make better ones. This will require changes to the content, process and context of sexbot development. Doing so will acknowledge the valuable role that technology can play in human sexuality, and allow us to challenge gendered norms and assumptions about male and female sexual desire. This will not be a panacea to the social problems that could arise from sexbot development, but it offers a more realistic and hopeful vision for the future of this technology in a pluralistic and progressive society

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.<p></p> Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).<p></p> Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.<p></p> Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

Deriving structure from evolution: metazoan segmentation

Segmentation is a common feature of disparate clades of metazoans, and its evolution is a central problem of evolutionary developmental biology. We evolved in silico regulatory networks by a mutation/selection process that just rewards the number of segment boundaries. For segmentation controlled by a static gradient, as in long-germ band insects, a cascade of adjacent repressors reminiscent of gap genes evolves. For sequential segmentation controlled by a moving gradient, similar to vertebrate somitogenesis, we invariably observe a very constrained evolutionary path or funnel. The evolved state is a cell autonomous ‘clock and wavefront' model, with the new attribute of a separate bistable system driven by an autonomous clock. Early stages in the evolution of both modes of segmentation are functionally similar, and simulations suggest a possible path for their interconversion. Our computation illustrates how complex traits can evolve by the incremental addition of new functions on top of pre-existing traits

To dash or to dawdle: verb-associated speed of motion influences eye movements during spoken sentence comprehension

In describing motion events verbs of manner provide information about the speed of agents or objects in those events. We used eye tracking to investigate how inferences about this verb-associated speed of motion would influence the time course of attention to a visual scene that matched an event described in language. Eye movements were recorded as participants heard spoken sentences with verbs that implied a fast (“dash”) or slow (“dawdle”) movement of an agent towards a goal. These sentences were heard whilst participants concurrently looked at scenes depicting the agent and a path which led to the goal object. Our results indicate a mapping of events onto the visual scene consistent with participants mentally simulating the movement of the agent along the path towards the goal: when the verb implies a slow manner of motion, participants look more often and longer along the path to the goal; when the verb implies a fast manner of motion, participants tend to look earlier at the goal and less on the path. These results reveal that event comprehension in the presence of a visual world involves establishing and dynamically updating the locations of entities in response to linguistic descriptions of events

Development of mental health first aid guidelines for deliberate non-suicidal self-injury: A Delphi study

<p>Abstract</p> <p>Background</p> <p>It is estimated that around 4% of the population engages, or has engaged, in deliberate non-suicidal self-injury. In clinical samples, the figures rise as high as 21%. There is also evidence to suggest that these figures may be increasing. A family member or friend may suspect that a person is injuring themselves, but very few people know how to respond if this is the case. Simple first aid guidelines may help members of the public assist people to seek and receive the professional help they require to overcome self-injury.</p> <p>Methods</p> <p>This research was conducted using the Delphi methodology, a method of reaching consensus in a panel of experts. Experts recruited to the panels included 26 professionals, 16 people who had engaged in self-injurious behaviour in the past and 3 carers of people who had engaged in self-injurious behaviour in the past. Statements about providing first aid to a person engaged in self-injurious behaviour were sought from the medical and lay literature, but little was found. Panel members were asked to respond to general questions about first aid for NSSI in a variety of domains and statements were extracted from their responses. The guidelines were written using the items most consistently endorsed by the consumer and professional panels.</p> <p>Results</p> <p>Of 79 statements rated by the panels, 18 were accepted. These statements were used to develop the guidelines appended to this paper.</p> <p>Conclusion</p> <p>There are a number of actions which are considered to be useful for members of the public when they encounter someone who is engaging in deliberate, non-suicidal self-injury. These guidelines will be useful in revising curricula for mental health first aid and NSSI first aid training programs. They can also be used by members of the public who want immediate information about how to assist a person who is engaging in such behaviour.</p

Identifying the 'Achilles heel' of type 1 diabetes.

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordWhen Thetis dipped her son Achilles into the River Styx to make him immortal, she held him by the heel, which was not submerged, and thus created a weak spot that proved deadly for Achilles. Millennia later, Achilles heel is part of today's lexicon meaning an area of weakness or a vulnerable spot that causes failure. Also implied is that an Achilles heel is often missed, forgotten or under-appreciated until it is under attack, and then failure is fatal. Paris killed Achilles with an arrow 'guided by the Gods'. Understanding the pathogenesis of type 1 diabetes (T1D) in order to direct therapy for prevention and treatment is a major goal of research into T1D. At the International Congress of the Immunology of Diabetes Society, 2018, five leading experts were asked to present the case for a particular cell/element that could represent 'the Achilles heel of T1D'. These included neutrophils, B cells, CD8+ T cells, regulatory CD4+ T cells, and enteroviruses, all of which have been proposed to play an important role in the pathogenesis of type 1 diabetes. Did a single entity emerge as 'the' Achilles heel of T1D? The arguments are summarized here, to make this case