Health Care Providers' Readiness to Adopt an Interactive 3D Web App in Consultations About Female Genital Mutilation/Cutting: Qualitative Evaluation of a Prototype.

BACKGROUND: Comprehensive and appropriate health care provision to women and girls with female genital mutilation or cutting (FGM/C) is lacking. Use of visuals in health care provider (HCP) consultations facilitates the communication of health information and its comprehension by patients. A web app featuring a 3D visualization of the genitourinary anatomy was developed to support HCPs in conferring clinical information about FGM/C to patients. OBJECTIVE: The aim of this study was to explore HCP perspectives on the use of visuals in discussion about FGM/C with their patients as well as to obtain their feedback on whether an interactive 3D web app showing the genitourinary anatomy would be helpful in patient consultations about FGM/C, identifying key features that are relevant to their clinical practice. METHODS: We evaluated the web app through a semistructured interview protocol with seven HCPs from various disciplines experienced in care for women and girls with FGM/C in migration-destination settings. Interviews were audio- and video-recorded for transcription, and were then analyzed thematically for contextualized data regarding HCPs' willingness to use a 3D web app visualizing anatomy in FGM/C consultations with patients. RESULTS: All but one of the seven participants expressed keen interest in using this web app and its 3D visuals of anatomy in FGM/C consultations with patients. Participants shared the common contexts for the use of visuals in health care for FGM/C and the concepts they are used to support, such as to help describe a patient's genitals after FGM/C and reinforce an understanding of clitoral anatomy, to illustrate the process of defibulation, or to explain the physiological effects of FGM/C. Participants also highlighted the benefit of using visuals that patients can relate to, expressing approval for the ability to customize the vulva by FGM/C subtype, skin tone, and complexity of the visual shown in the web app. Despite critiques that the visualization may serve to perpetuate idealistic standards for how a vulva should look, participants largely agreed on the web app's perceived usefulness to clinical practice and beyond. CONCLUSIONS: Evaluation of the web app developed in this study identified that digital tools with 3D models of the genitourinary anatomy that are accessible, informative, and customizable to any specific patient are likely to aid HCPs in communicating clinical information about FGM/C in consultations. Universal access to the web app may be particularly useful for HCPs with less experience in FGM/C. The app also prompts options for applications such as for personal use, in medical education, in patient medical records, or in legal settings. Further qualitative research with patients is required to confirm that adoption of the web app by HCPs in a consultation setting will indeed benefit patient care for women and girls with FGM/C.

Abnormal placental pathological findings and adverse clinical outcomes of oocyte donation.

We sought to assess chronic inflammatory responses in patients who achieved pregnancy by oocyte donation and non-oocyte donation-assisted reproductive technology and delivered at The Ottawa Hospital. Data describing maternal health, obstetrical outcomes, neonatal outcomes, and placental pathology were collected and analyzed from electronic medical records. An increased frequency of adverse obstetrical outcomes was observed. In the oocyte donation-assisted reproductive technology group, placental pathology data demonstrated increased frequency of fetal vascular malperfusion (p = 0.02) and placenta accreta (p < 0.001), representing a chronic inflammatory response. Placental pathology reflecting dysregulated immune processes and vasculopathy is associated with oocyte donation.

eLearning and Embryology: Designing an Application to Improve 3D Comprehension of Embryological Structures.

Embryology and histology are subjects that are viewed as particularly challenging by students in higher education. This negative perception is the result of many factors such as restricted access to lab facilities, lack of allocated time to these labs, and the complexity of the subject itself. One main factor that influences this viewpoint is the difficulty of grasping 3D orientation of sectioned tissues, especially regarding embryology. Attempts have been made previously to create alternative teaching methods to help alleviate these issues, but few have explored 3D visualisation. We aimed to address these issues by creating 3D embryological reconstructions from serial histology sections of a sheep embryo. These were deployed in a mobile application that allowed the user to explore the original sections in sequence, alongside the counterpart 3D model. The application was tested against a currently available eHistology programme on a cohort of life sciences graduates (n = 14) through qualitative surveys and quantitative testing through labelling and orientation-based tests. The results suggest that using a 3D modality such as the one described here significantly improves student comprehension of orientation of slides compared to current methods (p = 0.042). Furthermore, the developed application was deemed more interesting, useful, and usable than current eHistology tools (p < 0.05). Modalities such as that developed here could therefore provide a more effective approach to learning these challenging subjects potentially increasing student engagement with embryology and histology.

Virtual Anatomy Museum: Facilitating Public Engagement Through an Interactive Application.

Digitisation has become a common practice in the preservation of museum collections. Recent development of photogrammetry techniques allows for more accessible acquisition of three-dimensional (3D) models that serve as accurate representations of their originals. One of the potential applications of this is presenting digital collections as virtual museums to engage the public. Medical museums, particularly, would benefit from digitisation of their collections as many of them are closed to the public.The aim of this project was to design and create an interactive virtual museum which would represent the Anatomy Museum at the University of Glasgow with key specimens digitised using photogrammetry techniques. Members of the general public (25 participants) were asked to evaluate the usability and effectiveness of the interactive application by completing questionnaires.A process to digitise anatomical specimens using photogrammetry and convert them into game-ready 3D models was developed. The results demonstrated successful generation of 3D models of specimens preserved using different techniques, including specimens preserved in fluid and glass jars. User tests and evaluation of the application by members of the general public were positive, with participants agreeing that they would now consider visiting the real museum after using the virtual version.

Advancing Integrated Care through Practice Coaching.

INTRODUCTION: Practice coaches are skilled consultants who work in health care service delivery systems to make changes designed to improve patient outcomes, yet research is limited regarding their use to support integrated health care. This article describes the use of practice coaches in a large-scale effort to implement integrated care in the United States for patients with complex care needs. THEORY AND METHODS: This immersive, qualitative project involved five implementation team members; eight practice coaches; and 77 staff members from 12 health care organizations. Semistructured interviews were recorded and transcribed verbatim. Thematic and content analyses were applied in multiple stages to understand the use of practice coaches. RESULTS: Qualitative themes about the use of practice coaching in this initiative were: (a) development of "a very rich coaching model"; (b) moving from an organic to standardized coaching approach; and (c) coaches representing the "face of the initiative." DISCUSSION: A rich coaching model that includes an interdisciplinary coaching team can support integrated care transformation but challenges including finding highly qualified coaches and sustaining and disseminating the coaching model exist. Standardization was seen as a way to address such challenges. CONCLUSION: Practice coaches can provide individualized, hands-on guidance to support successful implementation of integrated care.

Improving Communication in Outpatient Consultations in People With Cirrhosis: The Development of a Question Prompt List (QPL).

BACKGROUND AND AIMS: Liver health professionals have difficulty discussing liver cirrhosis and its prognosis with patients and families. Question Prompt Lists (QPLs), which are evidence-based lists of "recommended questions," may improve communication but need to be designed specifically for the target population. This study aimed to develop and pilot a QPL for patients with cirrhosis. METHODS: A mixed-methods design in 3 phases. In phase 1 (item generation), potential questions for inclusion in the QPL were identified from 3 sources-a scoping literature review; an online survey; and interviews with patients, family members, and health professionals. In phase 2 (QPL construction), a multidisciplinary expert panel finalized the selection of questions and the format of the QPL. In phase 3 (pilot study), the QPL was assessed for acceptability and feasibility in a hepatology outpatient clinic population. RESULTS: From 258 topics initially identified, 30 questions were included in the first draft of the QPL. After review by a multidisciplinary expert panel including patients, the QPL was reduced to 22 questions. In the pilot study, 133/215 eligible patients consented to participate, although only 67/133 used the QPL in their clinic appointment. Among those who used the QPL, all questions were asked at least once. The most commonly asked question related to life expectancy. Most participants expressed support for the content of the QPL. CONCLUSIONS: A QPL, suitable for use in patients with liver cirrhosis attending hepatology outpatient clinics, has been developed and piloted. The QPL seems to be feasible to use and acceptable to patients and clinicians. Further work is needed to evaluate its effectiveness and to determine optimum delivery in clinical practice.

Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation.

Ageing is associated with attenuated autonomic function. Transcutaneous vagal nerve stimulation (tVNS) improved autonomic function in healthy young participants. We therefore investigated the effects of a single session of tVNS (studies 1 and 2) and tVNS administered daily for two weeks (study 3) in volunteers aged ≥ 55 years. tVNS was performed using modified surface electrodes on the tragus and connected to a transcutaneous electrical nerve stimulation (TENS) machine. Study 1: participants (n=14) received a single session of tVNS and sham. Study 2: all participants (n=51) underwent a single session of tVNS. Study 3: participants (n=29) received daily tVNS for two weeks. Heart rate variability and baroreflex sensitivity were derived. Quality of life (QoL), mood and sleep were assessed in study 3. tVNS promoted increases in measures of vagal tone and was associated with greater increases in baroreflex sensitivity than sham. Two weeks of daily tVNS improved measures of autonomic function, and some aspects of QoL, mood and sleep. Importantly, findings showed that improvements in measures of autonomic balance were more pronounced in participants with greater baseline sympathetic prevalence. This suggests it may be possible to identify individuals who are likely to encounter significant benefits from tVNS.

Analysis of building plumbing system flushing practices and communications.

Drinking water distribution system contamination incidents can prompt public agencies and drinking water utilities to issue do-not-drink and do-not-use advisories. After the contaminant is cleared from distribution mains, consumers are often directed to flush their plumbing. However, little validated guidance and few evaluated communications strategies are available on using flushing to decontaminate building water systems. Additionally, limited data support the effectiveness of current practices and recommendations. In this study, expert elicitation was used to assess existing flushing guidance and develop validated flushing guidance and communications for single-family residences. The resulting guidance recommends progressively opening all cold-water taps from the closest to point of entry to the furthest and allowing the water to run for at least 20 minutes. Hot-water taps should be opened progressively and run for at least 75 minutes. The guidance language and format conformed to grade-level and readability scores within recommended health communication ranges. The readability of eight other flushing guidance documents was also evaluated for contamination incidents from 2008-2015. Seven were written at a 10th-12th grade level, above the 6th-7th grade level recommended for health communications.

Using Photogrammetry to Create a Realistic 3D Anatomy Learning Aid with Unity Game Engine.

Learning and processing complex 3D structures can be challenging for students, particularly if relying on 2D images or if there is limited access to the study material. This applies to many fields including anatomy, where students report difficulty visualising complex structures such as the nervous system. We aimed to address this by creating a realistic model of part of the nervous system-the sympathetic nervous system which is known for the 'fight or flight' response. Photogrammetry was chosen to create a 3D digital model of a dissection of the sympathetic nervous system. The 3D model was then incorporated into an interactive learning aid that allowed users to manipulate the model and provided relevant text information and labels. Evaluation of the learning aid by students (n = 7) was positive with 71.4% strongly agreeing that using this application improved their understanding of the anatomy. The majority of students (85.7%) also agreed or strongly agreed that this application provided them with a view of the sympathetic nervous system that they had not seen before. Photogrammetry is a relatively simple and inexpensive method to create realistic 3D digital models that can promote self-directed learning and a greater understanding of complex structures.

Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation.

NEW FINDINGS: What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The review considers the pathways involved in eliciting the changes in autonomic balance seen with transcutaneous vagus nerve stimulation in relationship to other neuromodulatory techniques. The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non-invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised.

The effect of marital status on breast cancer-related outcomes in women under 65: A SEER database analysis.

BACKGROUND: Marital status is strongly associated with improved health and longevity. Being married has been shown to be positively associated with survival in patients with multiple different types of malignancy; however, little is known about the relationship between marital status and breast cancer in younger women. The purpose of this study is to investigate the effect of marital status on diagnosis, and survival of women under the age of 65 with breast cancer. METHODS: The SEER 18 regions database was used to identify women between the ages of 25-64 diagnosed with invasive breast cancer in the years 2004-2009. Logistic regression was used to predict later stage diagnosis by marital status and Cox proportional hazards models were used to compare breast cancer-related and all-cause survival by marital status classification. Models were stratified by AJCC stage. RESULTS: After adjusting for age, race, and ER status, unmarried women were 1.18 times more likely to be diagnosed at a later stage than married women (95% CI 1.15, 1.20). In adjusted analysis unmarried women were more likely to die of breast cancer and more likely to die of all causes than married women across all AJCC stages. CONCLUSIONS: Younger unmarried women with breast cancer may benefit from additional counseling, psychosocial support and case management at the time of diagnosis to ensure their overall outcomes are optimized.

Sociodemographic Factors Associated With Knowledge and Risk Perception of Human Papillomavirus and Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma Among a Predominantly Black Population.

Importance: The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing in the United States and may be underestimated among black individuals. Characterizing the current knowledge level among black individuals is critical to developing interventions to increase awareness. Objective: To describe the sociodemographic correlates of knowledge and risk perception of HPV and HPV-associated OPSCC among a predominantly black population. Design, Setting, and Participants: A cross-sectional survey was conducted at a drag racing event on September 12 and 13, 2015, in Madison, Illinois. The setting was a community-based oral head and neck cancer screening and education initiative. Participants were 301 drag race attendees 18 years or older who were conveniently sampled from attendees at an annual drag racing event predominantly patronized by black individuals. Main Outcomes and Measures: The primary outcome was knowledge and risk perception of HPV and HPV-associated OPSCC. An electronic-based questionnaire elicited sociodemographic information and contained oral cancer knowledge and risk perception items, which were combined to form knowledge and risk perception scores. Multivariable linear regression analysis assessed estimates of knowledge and risk perception of HPV and HPV-associated OPSCC. Results: Of the 301 participants (111 female and 190 male) completing the questionnaire, 194 (64.5%) were black. Overall, respondents ranged in age from 18 to 78 years, with a mean (SD) age of 48.0 (13.0) years. The mean (SD) knowledge score was 5.7 (4.6) of 15, and the mean (SD) risk perception score was 2.2 (1.4) of 6. Using multivariable linear regression, we found that, for every 1-year increase in age, knowledge of HPV-associated OPSCC decreased by 5.0% and was worse in men (ß = -1.26; 95% CI, -2.33 to -0.18), black vs white individuals (ß = -1.29; 95% CI, -2.35 to -0.23), and those with a high school diploma or less vs college graduates (ß = -3.23; 95% CI, -4.67 to -1.80). Black individuals also had lower perceived risk of developing HPV-associated OPSCC (ß = -0.36; 95% CI, -0.69 to -0.02) compared with white individuals, and participants with a high school diploma or less had lower perceived risk of developing HPV-associated OPSCC compared with those with a college degree or higher (ß = -0.59; 95% CI, -1.04 to -0.14). Conclusions and Relevance: Age and sex were independent correlates of knowledge of HPV-associated OPSCC, while race and education level were correlates of both knowledge and risk perception of HPV-associated OPSCC. These findings should inform future interventions targeted at increasing knowledge of HPV-associated OPSCC in black communities.

Short interfering RNA induced generation and translation of stable 5' mRNA cleavage intermediates.

Sequence-specific degradation of homologous mRNA is the main mechanism by which short-interfering RNAs (siRNAs) suppress gene expression. Generally, it is assumed that the mRNA fragments resulting from Ago2 cleavage are rapidly degraded, thus making the transcript translation-incompetent. However, the molecular mechanisms involved in the post-cleavage mRNA decay are not completely understood and the fate of cleavage intermediates has been poorly studied. Using specific siRNAs and short-hairpin RNAs (shRNAs) we show that the 5' and 3' mRNA cleavage fragments of human papilloma virus type 16 (HPV-16) E6/7 mRNA, over-expressed in cervical malignancies, are unevenly degraded. Intriguingly, the 5' mRNA fragment was more abundant and displayed a greater stability than the corresponding 3' mRNA fragment in RNAi-treated cells. Further analysis revealed that the 5' mRNA fragment was polysome-associated, indicating its active translation, and this was further confirmed by using tagged E7 protein to show that C-terminally truncated proteins were produced in treated cells. Overall, our findings provide new insight into the degradation of siRNA-targeted transcripts and show that RNAi can alter protein expression in cells as a result of preferential stabilization and translation of the 5' cleavage fragment. These results challenge the current model of siRNA-mediated RNAi and provide a significant step forward towards understanding non-canonical pathways of siRNA gene silencing.

PAT-seq: a method to study the integration of 3'-UTR dynamics with gene expression in the eukaryotic transcriptome.

A major objective of systems biology is to quantitatively integrate multiple parameters from genome-wide measurements. To integrate gene expression with dynamics in poly(A) tail length and adenylation site, we developed a targeted next-generation sequencing approach, Poly(A)-Test RNA-sequencing. PAT-seq returns (i) digital gene expression, (ii) polyadenylation site/s, and (iii) the polyadenylation-state within and between eukaryotic transcriptomes. PAT-seq differs from previous 3' focused RNA-seq methods in that it depends strictly on 3' adenylation within total RNA samples and that the full-native poly(A) tail is included in the sequencing libraries. Here, total RNA samples from budding yeast cells were analyzed to identify the intersect between adenylation state and gene expression in response to loss of the major cytoplasmic deadenylase Ccr4. Furthermore, concordant changes to gene expression and adenylation-state were demonstrated in the classic Crabtree-Warburg metabolic shift. Because all polyadenylated RNA is interrogated by the approach, alternative adenylation sites, noncoding RNA and RNA-decay intermediates were also identified. Most important, the PAT-seq approach uses standard sequencing procedures, supports significant multiplexing, and thus replication and rigorous statistical analyses can for the first time be brought to the measure of 3'-UTR dynamics genome wide.

Drinking water microbial myths.

Accounts of drinking water-borne disease outbreaks have always captured the interest of the public, elected and health officials, and the media. During the twentieth century, the drinking water community and public health organizations have endeavored to craft regulations and guidelines on treatment and management practices that reduce risks from drinking water, specifically human pathogens. During this period there also evolved misunderstandings as to potential health risk associated with microorganisms that may be present in drinking waters. These misunderstanding or "myths" have led to confusion among the many stakeholders. The purpose of this article is to provide a scientific- and clinically-based discussion of these "myths" and recommendations for better ensuring the microbial safety of drinking water and valid public health decisions.

Divergent reprogramming routes lead to alternative stem-cell states.

Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.

Genome-wide characterization of the routes to pluripotency.

Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator.

Reprogramming of somatic cells to induced pluripotent stem cells involves a dynamic rearrangement of the epigenetic landscape. To characterize this epigenomic roadmap, we have performed MethylC-seq, ChIP-seq (H3K4/K27/K36me3) and RNA-Seq on samples taken at several time points during murine secondary reprogramming as part of Project Grandiose. We find that DNA methylation gain during reprogramming occurs gradually, while loss is achieved only at the ESC-like state. Binding sites of activated factors exhibit focal demethylation during reprogramming, while ESC-like pluripotent cells are distinguished by extension of demethylation to the wider neighbourhood. We observed that genes with CpG-rich promoters demonstrate stable low methylation and strong engagement of histone marks, whereas genes with CpG-poor promoters are safeguarded by methylation. Such DNA methylation-driven control is the key to the regulation of ESC-pluripotency genes, including Dppa4, Dppa5a and Esrrb. These results reveal the crucial role that DNA methylation plays as an epigenetic switch driving somatic cells to pluripotency.