Exploring Whether and How People Experiencing High Deprivation Access Diagnostic Services: A Qualitative Systematic Review.

INTRODUCTION: To contribute to addressing diagnostic health inequalities in the United Kingdom, this review aimed to investigate determinants of diagnostic service use amongst people experiencing high deprivation in the United Kingdom. METHODS: A systematic review was conducted using three databases (EBSCO, Web of Science and SCOPUS) to search studies pertaining to diagnostic service use amongst people experiencing high deprivation. Search terms related to diagnostics, barriers and facilitators to access and deprivation. Articles were included if they discussed facilitators and/or barriers to diagnostic service access, contained participants' direct perspectives and focussed on individuals experiencing high deprivation in the United Kingdom. Articles were excluded if the full text was unretrievable, only abstracts were available, the research did not focus on adults experiencing high deprivation in the United Kingdom, those not including participants' direct perspectives (e.g., quantitative studies) and papers unavailable in English. RESULTS: Of 14,717 initial papers, 18 were included in the final review. Determinants were grouped into three themes (Beliefs and Behaviours, Emotional and Psychological Factors and Practical Factors), made up of 15 sub-themes. These were mapped to a conceptual model, which illustrates that Beliefs and Behaviours interact with Emotional and Psychological Factors to influence Motivation to access diagnostic services. Motivation then influences and is influenced by Practical Factors, resulting in a Decision to Access or Not. This decision influences Beliefs and Behaviours and/or Emotional and Psychological Factors such that the cycle begins again. CONCLUSION: Decision-making regarding diagnostic service use for people experiencing high deprivation in the United Kingdom is complex. The conceptual model illustrates this complexity, as well as the mediative, interactive and iterative nature of the process. The model should be applied in policy and practice to enable understanding of the factors influencing access to diagnostic services and to design interventions that address identified determinants. PATIENT OR PUBLIC CONTRIBUTION: Consulting lived experience experts was imperative in understanding whether and how the existing literature captures the lived experience of those experiencing high deprivation in South England. The model was presented to lived experience experts, who corroborated findings, highlighted significant factors for them and introduced issues that were not identified in the review.

Family presence during resuscitation: extending ethical norms from paediatrics to adults.

Many families of patients hold the view that it is their right to be present during a loved one's resuscitation, while the majority of patients also express the comfort and support they would feel by having them there. Currently, family presence is more commonly accepted in paediatric cardiopulmonary resuscitation (CPR) than adult CPR. Even though many guidelines are in favour of this practice and recognise potential benefits, healthcare professionals are hesitant to support adult family presence to the extent that paediatric family presence is supported. However, in this paper, we suggest that the ethical case to justify family presence during paediatric resuscitation (P-FPDR) is weaker than the justification of family presence during adult resuscitation (A-FPDR). We go on to support this claim using three main arguments that people use in clinical ethics to justify FPDR. These include scarcity of evidence documenting disruption, psychological benefits to family members following the incident and respect for patient autonomy. We demonstrate that these arguments actually apply more strongly to A-FPDR compared with P-FPDR, thereby questioning the common attitude of healthcare professionals of allowing the latter while mostly opposing A-FPDR. Importantly, we do not wish to suggest that P-FPDR should not be allowed. Rather, we suggest that since P-FPDR is commonly (and should be) allowed, so should A-FPDR. This is because the aforementioned arguments that are used to justify FPDR in general actually make a stronger case for A-FPDR.

Dlx5 and Dlx6 expression in the anterior neural fold is essential for patterning the dorsal nasal capsule.

Morphogenesis of the vertebrate facial skeleton depends upon inductive interactions between cephalic neural crest cells (CNCCs) and cephalic epithelia. The nasal capsule is a CNCC-derived cartilaginous structure comprising a ventral midline bar (mesethmoid) overlaid by a dorsal capsule (ectethmoid). Although Shh signalling from the anterior-most region of the endoderm (EZ-I) patterns the mesethmoid, the cues involved in ectethmoid induction are still undefined. Here, we show that ectethmoid formation depends upon Dlx5 and Dlx6 expression in a restricted ectodermal territory of the anterior neural folds, which we name NF-ZA. In both chick and mouse neurulas, Dlx5 and Dlx6 expression is mostly restricted to NF-ZA. Simultaneous Dlx5 and Dlx6 inactivation in the mouse precludes ectethmoid formation, while the mesethmoid is still present. Consistently, siRNA-mediated downregulation of Dlx5 and Dlx6 in the cephalic region of the early avian neurula specifically prevents ectethmoid formation, whereas other CNCC-derived structures, including the mesethmoid, are not affected. Similarly, NF-ZA surgical removal in chick neurulas averts ectethmoid development, whereas grafting a supernumerary NF-ZA results in an ectopic ectethmoid. Simultaneous ablation or grafting of both NF-ZA and EZ-I result, respectively, in the absence or duplication of both dorsal and ventral nasal capsule components. The present work shows that early ectodermal and endodermal signals instruct different contingents of CNCCs to form the ectethmoid and the mesethmoid, which then assemble to form a complete nasal capsule.

Pleural and pericardial effusions with cardiac conduction system and myocardial involvement: A rare presentation of sarcoidosis.

Sarcoidosis is a granulomatous immune disorder that can infiltrate many organ systems. When the cardiac system is involved, the myocardium and conduction system are frequently affected. We report the case of a patient presenting with complete heart block following cardioversion from atrial flutter accompanied by pleural and pericardial involvement whose diagnosis of sarcoidosis was subsequently made on pathological examination. Pericardial effusion and pleural effusion are rare manifestations of sarcoid, and the both of them happening simultaneously (less than 10 case reports) in conjunction with cardiac conduction system and myocardial involvement are almost nonexistent in the literature (one case report). As cardiac involvement in sarcoid can drastically increase the mortality, it is important to be vigilant for the diverse manifestations of cardiac involvement in all patients for which there is clinical suspicion of sarcoid.

Provider experiences of virtual reality in clinical treatment.

BACKGROUND: Virtual reality (VR) has proven effective in the treatment of specific phobias and trauma particularly when in-vivo exposure therapy might be costly (e.g. fear of flying, combat scenes). Similarly, VR has been associated with improvement of chronic pain and of acute pain during medical procedures. Despite its effectiveness as a healthcare tool, VR technology is not well-integrated into common practice. This qualitative study aims to explore the provider perception of the value of VR and identify barriers to VR implementation among healthcare providers. METHODS: A 66-item self-report survey was created to examine application of VR to clinical practice, perceived value of this treatment, ease of learning the technology, billing considerations, and other obstacles. 128 providers (MDs and PhDs) who were located in the United States and had used VR as a therapeutic tool in the past year were identified through research papers, as well as user lists and news articles from VR application websites. Of the 128 providers contacted, 17% (22) completed our online self-report measure. Of these, 13% of respondents (N = 17) completed greater than 75% of the questionnaire and were considered completers. Provider responses were collected over a one-month period and qualitatively analyzed. RESULTS: The majority of providers were from an academic institution (n = 12, 70.6%), and all providers practiced in the outpatient setting. Providers most commonly reported using VR for the treatment of acute pain and/or anxiety related to medical procedures (n = 11, 64.7%), followed by specific phobia (n = 6, 35.3%) and social phobia (n = 6, 35.3%). All providers agreed VR is a valuable tool they would recommend to colleagues. The majority (n = 15, 93.8%) believed VR helped their patients progress in treatment, compared with other methods. Providers cited the ability to individualize treatment (n = 14, 87.5%) and increase patient engagement (n = 15, 93.8%) as main benefits of VR. A minority reported negative feedback from patients about content (n = 4, 25%) or about the technology in general (n = 6, 37.5%), whereas all reported some form of positive feedback. The slight majority (n = 10, 58.8%) of providers did not find transitioning to VR difficult. Of those who did, cost was the most commonly cited barrier (n = 6). Regarding reimbursement, only 17.6% (n = 3) of providers reported the ability to bill for VR sessions. Most providers (n = 15, 88.2%) received training on their VR platform which they found beneficial. Comparing the trained and untrained groups found no significant difference in VR comfort level (p = 0.5058), the value of VR in practice (p = 0.551) or whether providers would recommend VR to others (p = 0.551), though sample sizes were small. CONCLUSIONS: In corroboration with previous research, this study demonstrates that VR is well-received by patients and providers, allowing increased patient engagement and treatment individualization. However, associated costs, including an inability to bill for this service, can present a barrier to further implementation. These findings will guide further development of virtual reality as a standardized tool in psychiatry and pain management.

OC-116, the chicken ortholog of mammalian MEPE found in eggshell, is also expressed in bone cells.

In chicken, ovocleidin 116 (OC-116) is found in the eggshell matrix and its encoding gene, OC-116, is expressed in uterine cells. In mammals, its orthologue MEPE encodes the matrix extracellular phosphoglycoprotein (MEPE), which has been shown to be involved in bone mineralization. Using RT-PCR and in situ hybridization on sections, we have checked whether OC-116 was also expressed in osteoblasts and osteocytes during bone development and mineralization in chicken embryos. We monitored OC-116 expression in the tibia and mandible of a growth series of chicken embryos from E3 to E19. Transcripts were identified in the osteoblasts as early as E5 in the tibia and E7 in the mandible, before matrix mineralization, then from these stages onwards in both the osteoblasts lining the mineralized bone matrix and the osteocytes. Therefore, early in chicken ontogeny and as soon as osteogenesis begins, OC-116 is involved. Its function, which remains still unknown, is maintained during further bone growth and mineralization, and later in adult, in which it is recruited for eggshell formation. We hypothesize that the ancestral OC-116/MEPE in a stem amniote was involved in these two functions and that the loss of eggshell in the mammalian lineage has probably favored the recruitment of some MEPE domains toward new functions in osteogenesis and mineralization, and in phosphatemia regulation.

Neural crest derivatives in ocular and periocular structures.

In vertebrates, the eye is an ectodermal compound structure associating neurectodermal and placodal anlagen. In addition, it benefits early on from a mesenchymal ectoderm-derived component, the neural crest. In this respect, the construction of chimeras between quail and chick has been a turning point, instrumental in appraising the contribution of the cephalic neural crest to the development of ocular and periocular structures. Given the variety of crest derivatives underscored in the developing eye, this study illustrates the fascinating ability of this unique structure to finely adapt its differentiation to microenvironmental cues. This analysis of neural crest cell contribution to ocular development emphasizes their paramount role to design the anterior segment of the eye, supply refracting media and contribute to the homeostasy of the anterior optic chamber.

Intraventricular 5,7-dihydroxytryptamine lesions disrupt acquisition of working memory task rules but not performance once learned.

The serotonergic system is implicated in learning and memory and its disorder, e.g. after 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") abuse. This study examined the effects of widespread depletion of serotonin (5-HT) using intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) on the learning of a working memory task in the dark agouti (DA) rat. The lesion impaired acquisition but not later performance of a nonspatial working memory rule, as measured using nonmatch to sample object recognition in the Y-maze. The lesion had a marginal effect on choice completion times over the course of testing. However, nonspecific effects did not provide a good account of the reduction in choice accuracy as this persisted when completion times were taken into account statistically. Similarly, in a second experiment, the same lesioned rats were slowed in the acquisition of spatial alternation in the T-maze. However, in the open field, there were no comparably long-lasting effects of the serotonergic depletion on line crossings and defecation, only a transient reduction in activity on the first day.Together, these data suggest that the serotonergic system is important in the acquisition of working memory tasks in the rat and that this outcome was unlikely to be the result of nonspecific effects of the lesion.

Endothelio-mesenchymal interaction controls runx1 expression and modulates the notch pathway to initiate aortic hematopoiesis.

Hematopoietic stem cells (HSCs) are produced by a small cohort of hemogenic endothelial cells (ECs) during development through the formation of intra-aortic hematopoietic cell (HC) clusters. The Runx1 transcription factor plays a key role in the EC-to-HC and -HSC transition. We show that Runx1 expression in hemogenic ECs and the subsequent initiation of HC formation are tightly controlled by the subaortic mesenchyme, although the mesenchyme is not a source of HCs. Runx1 and Notch signaling are involved in this process, with Notch signaling decreasing with time in HCs. Inhibiting Notch signaling readily increases HC production in mouse and chicken embryos. In the mouse, however, this increase is transient. Collectively, we show complementary roles of hemogenic ECs and mesenchymal compartments in triggering aortic hematopoiesis. The subaortic mesenchyme induces Runx1 expression in hemogenic-primed ECs and collaborates with Notch dynamics to control aortic hematopoiesis.

Sonic hedgehog signalling from foregut endoderm patterns the avian nasal capsule.

Morphogenesis of the facial skeleton depends on inductive interactions between cephalic neural crest cells and cephalic epithelia, including the foregut endoderm. We show that Shh expression in the most rostral zone of the endoderm, endoderm zone I (EZ-I), is necessary to induce the formation of the ventral component of the avian nasal capsule: the mesethmoid cartilage. Surgical removal of EZ-I specifically prevented mesethmoid formation, whereas grafting a supernumerary EZ-I resulted in an ectopic mesethmoid. EZ-I ablation was rescued by Shh-loaded beads, whereas inhibition of Shh signalling suppressed mesethmoid formation. This interaction between the endoderm and cephalic neural crest cells was reproduced in vitro, as evidenced by Gli1 induction. Our work bolsters the hypothesis that early endodermal regionalisation provides the blueprint for facial morphogenesis and that its disruption might cause foetal craniofacial defects, including those of the nasal region.

Patterning of the hyoid cartilage depends upon signals arising from the ventral foregut endoderm.

Hyoid bone is a part of the visceral skeleton which arises from both Hox-expressing (Hox+) and Hox-nonexpressing (Hox-) cephalic neural crest cells. In a previous work, we have demonstrated that the Hox- neural crest domain behaves as a naïve entity to which the ventral foregut endoderm confers patterning cues to specify the shape and orientation of the nasal and mandibular skeleton. By using ablation and grafting approaches, we have extended our study to the formation of the hyoid bone and tested the patterning ability of more caudal levels of the lateroventral foregut endoderm in the chick embryo at the early neurula stage. In this study, endodermal stripes have first been delineated according to the projection of mid- and posterior rhombencephalic structures. The extirpation of endodermal transverse stripes along the anteroposterior axis selectively hampers the formation of the ceratobranchials and epibranchials. Thus defined, the patterning ability of the endodermal stripes was further explored in their medial and lateral parts. When homotopically engrafted on the migration pathway of cephalic neural crest cells, ventromedial zones of endoderm lead to the formation of supernumerary basihyal and basibranchial, while lateral zones generate additional cartilaginous pieces recognizable as ceratobranchial and epibranchial. Taken together, our data demonstrate that, early in development, the ventral foregut endoderm exerts a regionalized patterning activity on the cephalic neural crest to build up the primary facial and visceral skeleton in jaws and neck and enable a map of the endodermal skeletogenic areas to be drawn. This map reveals that a cryptic metamerization of the anterior foregut endoderm precedes the formation of the branchial arches.

Msx genes are expressed in the carapacial ridge of turtle shell: a study of the European pond turtle, Emys orbicularis.

The turtle shell forms by extensive ossification of dermis ventrally and dorsally. The carapacial ridge (CR) controls early dorsal shell formation and is thought to play a similar role in shell growth as the apical ectodermal ridge during limb development. However, the molecular mechanisms underlying carapace development are still unknown. Msx genes are involved in the development of limb mesenchyme and of various skeletal structures. In particular, precocious Msx expression is recorded in skeletal precursors that develop close to the ectoderm, such as vertebral spinous processes or skull. Here, we have studied the embryonic expression of Msx genes in the European pond turtle, Emys orbicularis. The overall Msx expression in head, limb, and trunk is similar to what is observed in other vertebrates. We have focused on the CR area and pre-skeletal shell condensations. The CR expresses Msx genes transiently, in a pattern similar to that of fgf10. In the future carapace domain, the dermis located dorsal to the spinal cord expresses Msx genes, as in other vertebrates, but we did not see expansion of this expression in the dermis located more laterally, on top of the dermomyotomes. In the ventral plastron, although the dermal osseous condensations form in the embryonic Msx-positive somatopleura, we did not observe enhanced Msx expression around these elements. These observations may indicate that common mechanisms participate in limb bud and CR early development, but that pre-differentiation steps differ between shell and other skeletal structures and involve other gene activities than that of Msx genes.

Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton.

Diencephalic, mesencephalic and metencephalic neural crest cells are skeletogenic and derive from neural folds that do not express Hox genes. In order to examine the influence of Hox gene expression on skull morphogenesis, expression of Hoxa2, Hoxa3 and Hoxb4 in conjunction with that of the green fluorescent protein has been selectively targeted to the Hox-negative neural folds of the avian embryo prior to the onset of crest cell emigration. Hoxa2 expression precludes the development of the entire facial skeleton. Transgenic Hoxa2 embryos such as those from which the Hox-negative domain of the cephalic neural crest has been removed have no upper or lower jaws and no frontonasal structures. Embryos subjected to the forced expression of Hoxa3 and Hoxb4 show severe defects in the facial skeleton but not a complete absence of facial cartilage. Hoxa3 prevents the formation of the skeleton derived from the first branchial arch, but allows the development (albeit reduced) of the nasal septum. Hoxb4, by contrast, hampers the formation of the nasal bud-derived skeleton, while allowing that of a proximal (but not distal) segment of the lower jaw. The combined effect of Hoxa3 and Hoxb4 prevents the formation of facial skeletal structures, comparable with Hoxa2. None of these genes impairs the formation of neural derivatives of the crest. These results suggest that over the course of evolution, the absence of Hox gene expression in the anterior part of the chordate embryo was crucial in the vertebrate phylum for the development of a face, jaws and brain case, and, hence, also for that of the forebrain.

Interactions between Hox-negative cephalic neural crest cells and the foregut endoderm in patterning the facial skeleton in the vertebrate head.

The vertebrate face contains bones that differentiate from mesenchymal cells of neural crest origin, which colonize the median nasofrontal bud and the first branchial arches. The patterning of individual facial bones and their relative positions occurs through mechanisms that remained elusive. During the early stages of head morphogenesis, an endodermal cul-de-sac, destined to become Sessel's pouch, underlies the nasofrontal bud. Reiterative outpocketings of the foregut then form the branchial pouches. We have tested the capacity of endoderm of the avian neurula to specify the facial skeleton by performing ablations or grafts of defined endodermal regions. Neural crest cells that do not express Hox genes respond to patterning cues produced regionally in the anterior endoderm to yield distinct skeletal components of the upper face and jaws. However, Hox-expressing neural crest cells do not respond to these cues. Bone orientation is likewise dependent on the position of the endoderm relative to the embryonic axes. Our findings thus indicate that the endoderm instructs neural crest cells as to the size, shape and position of all the facial skeletal elements, whether they are cartilage or membrane bones.