Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures.

Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. Methods: We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.

Essential Principles to Create an Equitable, Inclusive, and Diverse EMS Workforce and Work Environment: A Position Statement and Resource Document.

POSITION STATEMENTEmergency medical services (EMS), similar to all aspects of health care systems, can play a vital role in examining and reducing health disparities through educational, operational, and quality improvement interventions. Public health statistics and existing research highlight that patients of certain socioeconomic status, gender identity, sexual orientation, and race/ethnicity are disproportionately affected with respect to morbidity and mortality for acute medical conditions and multiple disease processes, leading to health disparities and inequities. With regard to care delivery by EMS, research demonstrates that the current attributes of EMS systems may further contribute to these inequities, such as documented health disparities existing in EMS patient care management, and access along with EMS workforce composition not being representative of the communities served influencing implicit bias. EMS clinicians need to understand the definitions, historical context, and circumstances surrounding health disparities, health care inequities, and social determinants of health in order to reduce health care disparities and promote care equity. This position statement focuses on systemic racism and health disparities in EMS patient care and systems by providing multifaceted next steps and priorities to address these disparities and workforce development. NAEMSP believes that EMS systems should:Adopt a multifactorial approach to workforce diversity implemented at all levels within EMS agencies.Hire more diverse workforce by intentionally recruiting from marginalized communitiesIncrease EMS career pathway and mentorship programs within underrepresented minorities (URM) communities and URM-predominant schools starting at a young age to promote EMS as an achievable profession.Examine policies that promote systemic racism and revise policies, procedures, and rules to promote a diverse, inclusive, and equitable environment.Involve EMS clinicians in community engagement and outreach activities to promote health literacy, trustworthiness, and education.Require EMS advisory boards whose composition reflects the communities they serve and regularly audit membership to ensure inclusion.Increase knowledge and self-awareness of implicit/unconscious bias and acts of microaggression through established educational and training programs (i.e., anti- racism, upstander, and allyship) such that individuals recognize and mitigate their own biases and can act as allies.Redesign structure, content, and classroom materials within EMS clinician training programs to enhance cultural sensitivity, humility, and competency and to meet career development, career planning, and mentoring needs, particularly of URM EMS clinicians and trainees.Discuss cultural views that affect health care and medical treatment and the effects of social determinants of health on care access and outcomes during all aspects of training.Design research and quality improvement initiatives related to health disparities in EMS that are focused on racial/ethnic and gender inequities and include URM community leaders as essential stakeholders involved in all stages of research development and implementation.

Diversity, Equity, and Inclusion in the United States Emergency Medical Services Workforce: A Scoping Review.

OBJECTIVE: Emergency medical services (EMS) workforce demographics in the United States do not reflect the diversity of the population served. Despite some efforts by professional organizations to create a more representative workforce, little has changed in the last decade. This scoping review aims to summarize existing literature on the demographic composition, recruitment, retention, and workplace experience of underrepresented groups within EMS. METHODS: Peer-reviewed studies were obtained from a search of PubMed, CINAHL, Web of Science, ProQuest Thesis and Dissertations, and non-peer-reviewed ("gray") literature from 1960 to present. Abstracts and included full-text articles were screened by two independent reviewers trained on inclusion/exclusion criteria. Studies were included if they pertained to the demographics, training, hiring, retention, promotion, compensation, or workplace experience of underrepresented groups in United States EMS by race, ethnicity, sexual orientation, or gender. Studies of non-EMS fire department activities were excluded. Disputes were resolved by two authors. A single reviewer screened the gray literature. Data extraction was performed using a standardized electronic form. Results were summarized qualitatively. RESULTS: We identified 87 relevant full-text articles from the peer-reviewed literature and 250 items of gray literature. Primary themes emerging from peer-reviewed literature included workplace experience (n = 48), demographics (n = 12), workforce entry and exit (n = 8), education and testing (n = 7), compensation and benefits (n = 5), and leadership, mentorship, and promotion (n = 4). Most articles focused on sex/gender comparisons (65/87, 75%), followed by race/ethnicity comparisons (42/87, 48%). Few articles examined sexual orientation (3/87, 3%). One study focused on telecommunicators and three included EMS physicians. Most studies (n = 60, 69%) were published in the last decade. In the gray literature, media articles (216/250, 86%) demonstrated significant industry discourse surrounding these primary themes. CONCLUSIONS: Existing EMS workforce research demonstrates continued underrepresentation of women and nonwhite personnel. Additionally, these studies raise concerns for pervasive negative workplace experiences including sexual harassment and factors that negatively affect recruitment and retention, including bias in candidate testing, a gender pay gap, and unequal promotion opportunities. Additional research is needed to elucidate recruitment and retention program efficacy, the demographic composition of EMS leadership, and the prevalence of racial harassment and discrimination in this workforce.

Feasibility of Postmortem Imaging Assessment of Brain: Liver Volume Ratios with Pathological Validation.

INTRODUCTION: Organ volumes at postmortem magnetic resonance imaging (PMMR) should reflect autopsy organ weights, and thus brain:liver volume ratios on imaging could be a surrogate for weight volume ratios at autopsy to indicate fetal growth restriction (FGR). This study aims to determine whether imaging-based organ volume ratios can replace autopsy organ weight ratios. Materials and Meth ods: An unselected cohort of perinatal deaths underwent PMMR prior to autopsy. Semiautomated brain and liver volumes were compared to autopsy organ weights and ratios. Ratios were compared using Bland-Altman plots, and intra- and interobserver variability was assessed. RESULTS: A total 49 fetuses (25 male, 51%) at 17-42 weeks gestation were -assessed. There was a reasonable correlation between autopsy-derived brain:liver weight ratios (AB:LwR) and imaging-derived brain:liver volume ratios (IB:LvR; r = 0.8). The mean difference between AB:LwR and IB:LvR was +0.7 (95% limits of agreement range -1.5 to +2.9). In a small subset where FGR was present, the optimal IB:LvR ≥5.5 gave 83.3% sensitivity and 86.0% specificity for diagnosis. There was acceptable agreement within readers (mean difference in IB:LvRs 0.77 ± 2.21) and between readers -0.36 ± 0.68. CONCLUSION: IB:LvR provides a surrogate evaluation of AB:LwRs, and may be used as a marker of FGR where autopsy is declined.

Echogenic bowel in the second trimester - Where to from here?

Echogenic bowel is a 'soft marker' on prenatal ultrasound, which can be associated with a variety of conditions including chromosomal disorders, intrapartum infections, antepartum events and cystic fibrosis. Identification of this marker should prompt a further search for other soft markers, structural defects and placental abnormalities. We explore three cases of echogenic bowel identified on routine ultrasound scan. The first case highlights the potential for echogenic bowel to be a benign feature. Echogenic bowel was identified at eighteen weeks, which was attributed to intra-amniotic haemorrhage and consequent fetal ingestion of blood products. In contrast, the next two cases highlight the pathological causes of echogenic bowel. In case 2, echogenic bowel was identified at seventeen weeks with associated cystic hygromas. The fetus had positive testing for Turner syndrome, and notably, there was a family history of cystic fibrosis. The third case discusses a case of congenital cytomegalovirus infection, which was diagnosed with amniocentesis and maternal serology testing when echogenic bowel was identified. A review of the literature suggests that the risk of adverse outcomes is increased with the presence of multiple soft markers, associated deformities, poor growth, persistent echogenic bowel in the third trimester and increased echogenic resolution. Despite these factors, it is important to note the poor ultrasonographic sensitivity of less than 50% in neonates with congenital cytomegalovirus infection and the consequent importance of invasive testing. Therefore, we aim to propose an action plan for clinicians who identify echogenic bowel on prenatal scans in order to critically exclude detrimental pathology.

Turner syndrome - The clinical spectrum and management dilemmas.

INTRODUCTION: Turner syndrome (TS) is a common sex chromosome disorder, with a varied clinical spectrum and prognosis. It may range from the complete phenotype of TS characterised by short stature, ovarian failure, cardiac and renal abnormalities, with milder variants often associated with mosaic TS. MATERIALS AND METHODS: We describe five cases of TS. RESULTS: In case 1, complete TS was identified by first-trimester screening with a grossly oedematous fetus at 11 weeks of gestation and underwent medical termination of pregnancy due to the dismal prognosis. In case 2, a hydropic fetus and large cystic hygromas were identified at routine second-trimester morphology scan. Intra-uterine fetal death was identified at 22 weeks of gestation and formal karyotype confirmed complete TS. Case 3 demonstrates the potential for a successful live birth of mosaic TS with mild neurocognitive and renal abnormalities. Case 4 demonstrates the ability for TS to go undetected until adolescence where the patient was diagnosed at 15 years of age during investigations for severe anaemia, identified as secondary to critical aortic stenosis and Heyde's syndrome. Case 5 highlights the potential for patients with TS to reproduce with assisted reproductive technology. DISCUSSION: These cases explore the prognostic spectrum of TS and highlight that they have a potential to lead productive and fulfilling lives. CONCLUSION: Consequently, a multimodal risk stratification approach to prognostic counselling should be under-taken with consideration of pertinent history, major sonographic abnormalities, maternal serum testing and invasive testing.

Modification of the Thrombolysis in Myocardial Infarction risk score for patients presenting with chest pain to the emergency department.

OBJECTIVE: To develop a modified Thrombolysis in Myocardial Infarction (TIMI) score to effectively risk stratify patients presenting to the ED with chest pain. METHODS: A prospective observational study was conducted at two metropolitan EDs. Data were obtained during patient interview. The primary outcome was major adverse cardiovascular events (MACE) within 30 days of presentation. Two separate modifications of the TIMI score were developed. These scores were compared to the original TIMI in terms of the area under the receiver operating characteristic curve and diagnostic accuracy statistics (sensitivity, specificity, positive and negative predictive values). RESULTS: Of 1760 patients, 364 (20.7%) experienced 30 day MACE. The first modified TIMI score was a simplified TIMI (s-TIMI) including four variables: age ≥65 years, three or more risk factors, high-sensitivity troponin (hs-cTnI) and electrocardiogram changes. The second score included the same four variables plus two Global Registry of Acute Coronary Events (GRACE) variables (systolic blood pressure and estimated glomerular filtration rate). This score was termed the GRACE TIMI (g-TIMI). s-TIMI had a lower sensitivity compared to the original TIMI score (93.41 and 96.98%), but higher specificity (45.49 and 24.50%). The g-TIMI had a sensitivity of 98.90% and specificity of 14.90%. CONCLUSIONS: Attempts to modify the TIMI score yielded two scores with added predictive utility in comparison to the original TIMI model. The addition of GRACE variables (g-TIMI) increased sensitivity for MACE, but decreased the specificity of the model. The s-TIMI score yielded good specificity but had sensitivity that would not be acceptable by emergency physicians. The s-TIMI may be useful as part of an accelerated chest pain protocol.

African American Women's Perceptions on Access to Food and Water in Flint, Michigan.

OBJECTIVE: To explore the perceptions of food access by African American women in Flint, MI. METHODS: Using womanist theory, in which African American women's experiential knowledge centered the analysis, 8 focus groups were conducted during fall/spring, 2014-2015. Seventeen mothers aged 21-50 years with children aged <18 years and 13 women aged >60 years comprised the groups. RESULTS: The high cost of water, poor availability of healthy foods in inner-city stores, and limited transportation were barriers to accessing healthy food. Conversely, receiving food from food giveaways, friends, and family, as well as access to transportation facilitated food access. These women also reported discriminatory experiences and diet-related health concerns. Participants were keenly aware of available free community resources and gender, racial, and income barriers to accessing them. CONCLUSION AND IMPLICATIONS: Understanding these barriers and facilitators provides information to aid local food policy assistance decisions and inform community-based interventions, especially given the lead contamination of water and the purported importance of a healthy diet to sequester lead.

A qualitative study to understand positive and negative child feeding behaviors of immigrant Asian Indian mothers in the US.

To understand current practice of child feeding behaviors, and underlying factors influencing these practices in Asian Indian mothers, qualitative in-depth interviews were conducted with 27 immigrant Asian Indian mothers of children ages 5-10 years. Using the theory of planned behavior as a guiding framework, child feeding behaviors employed, beliefs about the outcomes of feeding behaviors, perceived ease or difficultly in practicing feeding behaviors, and social norms were explored during the interviews. Thematic analysis was conducted using coding and display matrices. Mothers were motivated by nutrition outcomes when practicing positive and negative controlling feeding behaviors. Outcomes related to preservation of Indian culture and values also influenced feeding behaviors. Pressuring to eat was often practiced despite the perception of ineffectiveness. Use of food rewards was found, and use of TV to control children's food intake despite the clear understanding of undesirable nutrition outcomes was a unique finding. Asian Indian mothers need effective child feeding strategies that are culturally appropriate. Integrating cultural beliefs in nutrition education could help support existing motivation and behavior modification.

Hydroxyapatite as a carrier for bone morphogenetic protein.

Bone morphogenetic proteins (BMPs) can induce the formation of new bone in numerous orthopedic and dental applications in which loss of bone is the main issue. The combination of BMP with a biomaterial that can carry and deliver proteins has been demonstrated to maximize the therapeutic effects of BMPs. However, no ideal candidate with optimal characteristics as a carrier has emerged for clinical use of BMPs. Hydroxyapatite (HA) is a potential BMP carrier with its osteoconductive properties and desirable characteristics as a bone graft biomaterial. In this study, 3 different methods to load BMP into HA materials were characterized and compared based on the BMP uptake and release profile. BMP was loaded into HA in 3 ways: (1) incorporation of BMP during HA precipitation, (2) HA immersion in BMP solution, and (3) BMP incorporation during dicalcium phosphate dihydrate (DCPD) conversion to HA. The size of HA crystals decreased when BMP was loaded during HA precipitation and HA immersion in BMP solution; however, it did not change when BMP was loaded during DCPD-to-HA conversion. The highest BMP uptake was achieved using the immersion method followed by HA precipitation, and the lowest via DCPD conversion. It is interesting to note that BMP loading during HA precipitation resulted in sustained and prolonged BMP release compared with the 2 other BMP loading methods. In conclusion, BMP incorporation during HA precipitation revealed itself to be the best loading method.

Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice.

OBJECTIVE: To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA). METHODS: Double-heterozygous (type XI collagen-deficient [Col11a1(+/-)] and Ddr2-deficient [Ddr2(+/-)]) mutant mice were generated. Knee joints of Ddr2(+/-) mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry. RESULTS: The rate of progressive degeneration in knee joints was dramatically reduced in the double-heterozygous mutant mice compared with that in the type XI collagen-deficient mice. The progression in the double-heterozygous mutant mice was delayed by ∼6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2(+/-) mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13. CONCLUSION: Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus.

Randomized trials published in the journal of dental research are cited more often compared with those in other top-tier non-specialty-specific dental journals.

BACKGROUND AND AIM: Randomized controlled trials (RCTs) are viewed as the gold standard for clinical research. Oftentimes the citation counts serve as an important measure for assessing the significance of an RCT to promote the dissemination of science. This study attempts to identify the factors associated with the number of times RCTs are cited within the first 24 months since publication. MATERIALS AND METHODS: RCTs published between January 1, 2002, and November 30, 2006, in 4 journals (Journal of Dental Research, European Journal of Oral Sciences, Journal of Dentistry, and Clinical Oral Investigations) were selected for analysis. Citation counts of RCTs in the first 24 months since publication was the outcome variable. The independent variables included journal of publication, geographic region of origin of study, number of authors, financial support, number of references, presentation of a statistically significant result, and if the study was conducted on animals. Bivariate associations between the outcome and independent variables were examined by Kruskal-Wallis test, Mann-Whitney U test, and Spearman rank correlations where appropriate. A multivariable negative binomial regression model was also built to examine the association. RESULTS: A total of 163 RCTs were selected for analysis. The mean citation count for the first 24 months count was 2.61. Close to 20% of RCTs were not cited even once in this observation period. RCTs published in the highest impact factor journal (Journal of Dental Research) tended to be cited most often (P < .05). CONCLUSION: Based on our initial analysis of 4 journals, publishing randomized trials in high-impact journals will likely provide better dissemination of research findings.

Parental influences on dairy intake in children, and their role in child calcium-fortified food use.

OBJECTIVE: To understand how parental influences on dairy food intake relate to early adolescent children's use of calcium-fortified food. DESIGN: Content analysis of qualitative interviews to identify parental influences on dairy intake; calcium-fortified food survey to identify children as either calcium-fortified food users or nonusers. SETTING AND PARTICIPANTS: A convenience sample of Asian (n = 56), Hispanic (n = 61), and white (n = 74) parents of children 10-13 years old, including boys (n = 86) and girls (n = 105). VARIABLES MEASURED AND ANALYSIS: Cluster analysis to identify groups with similar coded parental influences and chi-square analysis to determine associations between these groups and calcium-fortified food use. RESULTS: Two dominant patterns of parental influences: Cluster 1 (n = 128), with positive parental influences related to availability of dairy, milk, and cheese; positive health beliefs for dairy, and child preferences for dairy and cheese, included parents whose children were more likely to use calcium-fortified food. Cluster 2 (n = 63), with positive influences for availability of dairy and milk, included parents whose children were equally likely to be either users or nonusers of calcium-fortified food (P < .05). CONCLUSION: Strategies to improve parental influence on children's dairy intake might also encourage calcium-fortified food intake and improve calcium nutriture.

The role of power, process, and relationships in participatory research for statewide HIV/AIDS programming.

This paper presents a case study of a participatory process that was used to understand the needs of persons living with HIV/AIDS in a US state. The case illustrates that participation in a community-based research project is a dynamic phenomenon that must be negotiated among an evolving web of roles and relationships. Using a continuum to model the multiple modes of community participation, we follow the changing nature of participation over the course of a single project. Our analysis illustrates the different levels of participation given by the continuum as well as the dynamic nature of participation. A shared understanding of participation evolves as the roles and relationships of those involved are negotiated and renegotiated. However, lack of reflection over power differentials can lead to disempowering outcomes even after achieving a seemingly participatory process. The case reveals that failing to resolve divergent assumptions about power and purpose can lead to fissures that are difficult to overcome.