Epithelial-like transport of mineral distinguishes bone formation from other connective tissues.

We review unique properties of bone formation including current understanding of mechanisms of bone mineral transport. We focus on formation only; mechanism of bone degradation is a separate topic not considered. Bone matrix is compared to other connective tissues composed mainly of the same proteins, but without the specialized mechanism for continuous transport and deposition of mineral. Indeed other connective tissues add mechanisms to prevent mineral formation. We start with the epithelial-like surfaces that mediate transport of phosphate to be incorporated into hydroxyapatite in bone, or in its ancestral tissue, the tooth. These include several phosphate producing or phosphate transport-related proteins with special expression in large quantities in bone, particularly in the bone-surface osteoblasts. In all connective tissues including bone, the proteins that constitute the protein matrix are mainly type I collagen and γ-carboxylate-containing small proteins in similar molar quantities to collagen. Specialized proteins that regulate connective tissue structure and formation are surprisingly similar in mineralized and non-mineralized tissues. While serum calcium and phosphate are adequate to precipitate mineral, specialized mechanisms normally prevent mineral formation except in bone, where continuous transport and deposition of mineral occurs.

Growth and mineralization of osteoblasts from mesenchymal stem cells on microporous membranes: Epithelial-like growth with transmembrane resistance and pH gradient.

Osteoblasts in vivo form an epithelial-like layer with tight junctions between cells. Bone formation involves mineral transport into the matrix and acid transport to balance pH levels. To study the importance of the pH gradient in vitro, we used Transwell inserts composed of polyethylene terephthalate (PET) membranes with 0.4 µm pores at a density of (2 ± 0.4) x 106 pores per cm2. Mesenchymal stem cells (MSCs) prepared from murine bone marrow were used to investigate alternative conditions whereby osteoblast differentiation would better emulate in vivo bone development. MSCs were characterized by flow cytometry with more than 90% CD44 and 75% Sca-1 labeling. Mineralization was validated with paracellular alkaline phosphatase activity, collagen birefringence, and mineral deposition confirming MSCs identity. We demonstrate that MSCs cultured and differentiated on PET inserts form an epithelial-like layer while mineralizing. Measurement of the transepithelial resistance was ∼1400 Ω•cm2 at three weeks of differentiation. The pH value of the media above and under the cells were measured while cells were in proliferation and differentiation. In mineralizing cells, a difference of 0.145 pH unit was observed between the medium above and under the cells indicating a transepithelial gradient. A significant difference in pH units was observed between the medium above and below the cells in proliferation compared to differentiation. Data on pH below membranes were confirmed by pH-dependent SNARF1 fluorescence. Control cells in proliferative medium did not form an epithelial-like layer, displayed low transepithelial resistance, and there was no significant pH gradient. By transmission electron microscopy, membrane attached osteoblasts in vitro had abundant mitochondria consistent with active transport that occurs in vivo by surface osteoblasts. In keeping with osteoblastic differentiation, scanning electron microscopy identified deposition of extracellular collagen surrounded by hydroxyapatite. This in vitro model is a major advancement in modeling bone in vivo for understanding of osteoblast bone matrix production.

Cellular and extracellular matrix of bone, with principles of synthesis and dependency of mineral deposition on cell membrane transport.

Bone differs from other connective tissues; it is isolated by a layer of osteoblasts that are connected by tight and gap junctions. This allows bone to create dense lamellar type I collagen, control pH, mineral deposition, and regulate water content forming a compact and strong structure. New woven bone formed after degradation of mineralized cartilage is rapidly degraded and resynthesized to impart structural order for local bone strength. Ossification is regulated by thickness of bone units and by patterning via bone morphogenetic receptors including activin, other bone morphogenetic protein receptors, transforming growth factor-ß receptors, all part of a receptor superfamily. This superfamily interacts with receptors for additional signals in bone differentiation. Important features of the osteoblast environment were established using recent tools including osteoblast differentiation in vitro. Osteoblasts deposit matrix protein, over 90% type I collagen, in lamellae with orientation alternating parallel or orthogonal to the main stress axis of the bone. Into this organic matrix, mineral is deposited as hydroxyapatite. Mineral matrix matures from amorphous to crystalline hydroxyapatite. This process includes at least two-phase changes of the calcium-phosphate mineral as well as intermediates involving tropocollagen fibrils to form the bone composite. Beginning with initiation of mineral deposition, there is uncertainty regarding cardinal processes, but the driving force is not merely exceeding the calcium-phosphate solubility product. It occurs behind a epithelial-like layer of osteoblasts, which generate phosphate and remove protons liberated during calcium-phosphate salt deposition. The forming bone matrix is discontinuous from the general extracellular fluid. Required adjustment of ionic concentrations and water removal from bone matrix are important details remaining to be addressed.

Toxin Enzyme Immunoassays Detect Clostridioides difficile Infection With Greater Severity and Higher Recurrence Rates.

BACKGROUND: Few data suggest that Clostridioides difficile infections (CDIs) detected by toxin enzyme immunoassay (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAATs) only. We compared toxin- positive and NAAT-positive-only CDI across geographically diverse sites. METHODS: A case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases were detected during 2014-2015 by a testing algorithm (specimens initially tested by glutamate dehydrogenase and toxin EIA; if discordant results, specimens were reflexed to NAAT) and classified as toxin positive or NAAT positive only. Medical charts were reviewed. Multivariable logistic regression models were used to compare CDI-related complications, recurrence, and 30-day mortality between the 2 groups. RESULTS: Of 4878 cases, 2160 (44.3%) were toxin positive and 2718 (55.7%) were NAAT positive only. More toxin-positive than NAAT-positive-only cases were aged ≥65 years (48.2% vs 38.0%; P < .0001), had ≥3 unformed stools for ≥1 day (43.9% vs 36.6%; P < .0001), and had white blood cell counts ≥15 000 cells/µL (31.4% vs 21.4%; P < .0001). In multivariable analysis, toxin positivity was associated with recurrence (adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.61-2.23), but not with CDI-related complications (aOR, 0.91; 95% CI, .67-1.23) or 30-day mortality (aOR, 0.95; 95% CI, .73-1.24). CONCLUSIONS: Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive-only CDI that were detected by an algorithm that utilized an initial glutamate dehydrogenase screening test.

Estimating Risk to Responders Exposed to Avian Influenza A H5 and H7 Viruses in Poultry, United States, 2014-2017.

In the United States, outbreaks of avian influenza H5 and H7 virus infections in poultry have raised concern about the risk for infections in humans. We reviewed the data collected during 2014-2017 and found no human infections among 4,555 exposed responders who were wearing protection.

Support of bone mineral deposition by regulation of pH.

Osteoblasts secrete collagen and isolate bone matrix from extracellular space. In the matrix, alkaline phosphatase generates phosphate that combines with calcium to form mineral, liberating 8 H+ per 10 Ca+2 deposited. However, pH-dependent hydroxyapatite deposition on bone collagen had not been shown. We studied the dependency of hydroxyapatite deposition on type I collagen on pH and phosphate by surface plasmon resonance in 0-5 mM phosphate at pH 6.8-7.4. Mineral deposition saturated at <1 mM Ca2+ but was sensitive to phosphate. Mineral deposition was reversible, consistent with amorphous precipitation; stable deposition requiring EDTA removal appeared with time. At pH 6.8, little hydroxyapatite deposited on collagen; mineral accumulation increased 10-fold at pH 7.4. Previously, we showed high expression Na+/H+ exchanger (NHE) and ClC transporters in osteoblasts. We hypothesized that, in combination, these move protons across osteoblasts to the general extracellular space. We made osteoblast membrane vesicles by nitrogen cavitation and used acridine orange quenching to characterize proton transport. We found H+ transport dependent on gradients of chloride or sodium, consistent with apical osteoblast ClC family Cl-,H+ antiporters and basolateral osteoblast NHE family Na+/H+ exchangers. Little, if any, active H+ transport, supported by ATP, occurred. Major transporters include cariporide-sensitive NHE1 in basolateral membranes and ClC3 and ClC5 in apical osteoblast membranes. The mineralization inhibitor levamisole reduced bone formation and expression of alkaline phosphatase, NHE1, and ClC5. We conclude that mineral deposition in bone collagen is pH-dependent, in keeping with H+ removal by Cl-,H+ antiporters and Na+/H+-exchangers. Periodic orientation hydroxyapatite is organized on type I collagen-coiled coils.

TRPC6 channel translocation into phagosomal membrane augments phagosomal function.

Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H(+) into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired.

Identification of Approaches to Improve Patient Trust in Health Systems: A Group Concept Mapping Study.

EXECUTIVE SUMMARY: Higher levels of institutional trust have been associated with increased preventive healthcare use, greater adherence to treatment plans, and improved overall self-rated health status. However, little attention has been paid to understanding approaches to improve patient institutional trust. This study used group concept mapping to elicit patient perspectives on ways to improve patient trust. Eighteen insured individuals living in Delaware County, Pennsylvania, participated in the concept mapping sessions. Participants first brainstormed in a group setting to develop a list of ideas about how systems could improve trust, then each participant sorted the ideas into thematic domains and rated the statements based on both importance and feasibility. Four primary domains for improving institutional trust emerged: privacy, patient-provider relationship, respect for patients, and health system guidelines. Multiple action items to improve patient trust of the system were provided for each domain, and participants rated the "privacy" domain as the most feasible and important to address.We suggest that future local efforts to build institutional trust implement processes to improve the protection of patient privacy, support patient-provider relationships, and engender respect for patients, and that institutions develop system-level guidelines to support these principles. Next steps involve exploring the importance of these domains across other populations and developing and testing targeted interventions.

Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.

Serious Psychological Distress and Smoking During Pregnancy in the United States: 2008-2014.

INTRODUCTION: The current study examined the relationship between acute (past 30 day) and recent (past year but not past 30 day) serious psychological distress (SPD) and smoking during pregnancy among women in the United States overall, stratified by demographic characteristics, and described the change in the prevalence of prenatal smoking among women with and without SPD, from 2008 to 2014. METHODS: Data were drawn from the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional study of US persons aged 12 and over. SPD and smoking in the past 30 days among pregnant women, aged 18 and older, were examined using logistic regression models. Heterogeneity in this association by demographic characteristics, trends over time, and level of cigarette consumption was also examined. RESULTS: Prenatal smoking was common. Almost 40% of pregnant women with acute SPD reported smoking, 23% of pregnant women with recent SPD smoked, and 11.7% of pregnant women without recent SPD smoked. No significant change was found in the prevalence of prenatal smoking from 2008 to 2014 in any of these groups. Robust relationships were found between acute (OR = 5.05 [3.64-6.99]) and recent SPD (OR = 2.37 [1.74-3.24]) and smoking; these findings remained after adjusting for demographics. CONCLUSIONS: SPD and smoking during pregnancy are strongly associated; this relationship is present across all sociodemographic groups and the prevalence of smoking in pregnancy has remained relatively unchanged over the past decade both in the presence and absence of SPD. IMPLICATIONS: SPD and smoking in pregnancy are robustly linked; the prevalence of smoking in pregnancy is extremely high in women with SPD. Screening women with mental health problems for prenatal smoking, as well as screening pregnant smokers for mental health problems, seems warranted and may assist more women in seeking and utilizing treatment options. Efforts to reduce the prevalence of smoking during pregnancy might specifically target women with SPD, where the potential for impact is substantial.

DEVELOPMENT AND VALIDATION OF A NOVEL TOOL TO PREDICT HOSPITAL READMISSION RISK AMONG PATIENTS WITH DIABETES.

OBJECTIVE: To develop and validate a tool to predict the risk of all-cause readmission within 30 days (30-d readmission) among hospitalized patients with diabetes. METHODS: A cohort of 44,203 discharges was retrospectively selected from the electronic records of adult patients with diabetes hospitalized at an urban academic medical center. Discharges of 60% of the patients (n = 26,402) were randomly selected as a training sample to develop the index. The remaining 40% (n = 17,801) were selected as a validation sample. Multivariable logistic regression with generalized estimating equations was used to develop the Diabetes Early Readmission Risk Indicator (DERRI™). RESULTS: Ten statistically significant predictors were identified: employment status; living within 5 miles of the hospital; preadmission insulin use; burden of macrovascular diabetes complications; admission serum hematocrit, creatinine, and sodium; having a hospital discharge within 90 days before admission; most recent discharge status up to 1 year before admission; and a diagnosis of anemia. Discrimination of the model was acceptable (C statistic 0.70), and calibration was good. Characteristics of the validation and training samples were similar. Performance of the DERRI™ in the validation sample was essentially unchanged (C statistic 0.69). Mean predicted 30-d readmission risks were also similar between the training and validation samples (39.3% and 38.7% in the highest quintiles). CONCLUSION: The DERRI™ was found to be a valid tool to predict all-cause 30-d readmission risk of individual patients with diabetes. The identification of high-risk patients may encourage the use of interventions targeting those at greatest risk, potentially leading to better outcomes and lower healthcare costs. ABBREVIATIONS: DERRI™ = Diabetes Early Readmission Risk Indicator ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification GEE = generalized estimating equations ROC = receiver operating characteristic.

The Gestational Vaginal Microbiome and Spontaneous Preterm Birth among Nulliparous African American Women.

Introduction Early markers to identify pregnant women at high risk for spontaneous preterm birth (SPTB) have not been established and preventive options are limited. Recent attention has focused on examining the importance of characterizing the vaginal microbiome to predict SPTB. Results We examined the diversity and structure of the vaginal microbiome in nulliparous African American women during early pregnancy and compared 13 women who delivered preterm and 27 women who delivered at term. Samples were taken at one of two points in gestation, before 16 weeks or between 20 and 24 weeks. Among women who delivered preterm, we found lower bacterial diversity with lower abundance of Coriobacteriaceae, Sneathia, Prevotella, and Aerococcus compared with women delivering at term (linear discriminant analysis score > 3.0). The Shannon diversity index was not significantly different between the groups (p-value = 0.239). Phylogenetic diversity and Chao1 suggested a lower diversity in the vaginal microbiota of women who delivered preterm compared with term, but these findings were not significantly different (p = 0.077 and p = 0.066, respectively). Conclusion These data suggest that the vaginal microbiome of women delivering preterm had lower diversity than women delivering after 37 weeks, although these findings need to be explored in a larger sample of nulliparous African American women.

The role of the bacterial microbiota on reproductive and pregnancy health.

Recent assessments have examined the composition of bacterial communities influencing reproductive, pregnancy and infant health. The Microbiome Project has made great strides in sequencing the microbiome and identifying the vast communities of microorganisms that inhabit our bodies and much work continues to examine the individual contribution of bacteria on health and disease to inform future therapies. This review explores the current literature outlining the contribution of important bacteria on reproductive health among sexually active men and women, outlines gaps in current research to determine causal and interventional relationships, and suggests future research initiatives. Novel treatments options to reduce adverse outcomes must recognize the heterogeneity of the bacteria within the microbiome and adequately assess long-term benefits in reducing disease burden and re-establishing a healthy Lactobacillus-dominant state. Recognizing other reservoirs outside of the lower genital track and within sexual partners as well as genetic and individual moderators may be most important for long-term cure and reduction of disease. It will be important to develop useful screening tools and comprehensively examine novel therapeutic options to promote the long-term reduction of high-risk bacteria and the re-establishment of healthy bacterial levels to considerably improve outcomes among pregnant women and sexually active men and women.

Predicting dredging-associated effects to coral reefs in Apra Harbor, Guam - Part 2: Potential coral effects.

Coral reefs are in decline worldwide due to anthropogenic stressors including reductions in water and substratum quality. Dredging results in the mobilization of sediments, which can stress and kill corals via increasing turbidity, tissue damage and burial. The Particle Tracking Model (PTM) was applied to predict the potential impacts of dredging-associated sediment exposure on the coral reef ecosystems of Apra Harbor, Guam. The data were interpreted using maps of bathymetry and coral abundance and distribution in conjunction with impact parameters of suspended sediment concentration (turbidity) and sedimentation using defined coral response thresholds. The results are presented using a "stoplight" model of negligible or limited impacts to coral reefs (green), moderate stress from which some corals would be expected to recover while others would not (yellow) and severe stress resulting in mortality (red). The red conditions for sediment deposition rate and suspended sediment concentration (SSC) were defined as values exceeding 25 mg cm(-2) d(-1) over any 30 day window and >20 mg/l for any 18 days in any 90 day period over a column of water greater than 2 m, respectively. The yellow conditions were defined as values >10 mg cm(-2) d(-1) and <25 mg cm(-2) d(-1) over any 30 day period, and as 20% of 3 months' concentration exceeding 10 mg/l for the deposition and SSC, respectively. The model also incorporates the potential for cumulative effects on the assumption that even sub-lethal stress levels can ultimately lead to mortality in a multi-stressor system. This modeling approach can be applied by resource managers and regulatory agencies to support management decisions related to planning, site selection, damage reduction, and compensatory mitigation.

Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission.

Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds--United States, December 2014-January 2015.

During December 15, 2014-January 16, 2015, the U.S. Department of Agriculture received 14 reports of birds infected with Asian-origin, highly pathogenic avian influenza A (HPAI) (H5N2), (H5N8), and (H5N1) viruses. These reports represent the first reported infections with these viruses in U.S. wild or domestic birds. Although these viruses are not known to have caused disease in humans, their appearance in North America might increase the likelihood of human infection in the United States. Human infection with other avian influenza viruses, such as HPAI (H5N1) and (H5N6) viruses and (H7N9) virus, has been associated with severe, sometimes fatal, disease, usually following contact with poultry.

First Trimester Levels of BV-Associated Bacteria and Risk of Miscarriage Among Women Early in Pregnancy.

OBJECTIVES: Prior studies have examined the role of bacterial vaginosis (BV) and increased risk of miscarriage; however the risk has been modest and many BV positive pregnant women deliver at term. BV is microbiologically heterogeneous, and thus the identification of specific BV-associated bacteria associated with miscarriage is warranted. METHODS: We measured the presence and level of seven BV-associated bacteria prior to 14 weeks gestation among urban pregnant women seeking routine prenatal care at five urban obstetric practices at Temple University Hospital in Philadelphia PA from July 2008 through September 2011. 418 Pregnant women were included in this assessment and 74 experienced a miscarriage. RESULTS: Mean log concentration of BVAB3 was significantly higher among women experiencing a miscarriage (4.27 vs. 3.71, p value = 0.012). Younger women with high levels of BVAB3 had the greatest risk of miscarriage. In addition, we found a significant decreased risk of miscarriage among women with higher log concentrations of Leptotrichia/Sneathia species or Megasphaera phylotype 1-like species early in pregnancy. CONCLUSIONS FOR PRACTICE: The identification of selected vaginal bacteria associated with an increased risk of miscarriage could support screening programs early in pregnancy and promote early therapies to reduce early pregnancy loss.

Early pregnancy changes in bacterial vaginosis-associated bacteria and preterm delivery.

BACKGROUND: We evaluated the importance of measuring early vaginal levels of eight bacterial vaginosis (BV)-associated bacteria, at two points in pregnancy, and the risk of spontaneous preterm delivery (SPTD) among pregnant women and the subgroup of pregnant women with a history of preterm delivery (PTD). METHODS: This prospective cohort study enrolled women at five urban obstetric practices at Temple University Hospital in Philadelphia PA. Women with singleton pregnancies less than 16 weeks gestation self-collected vaginal swabs at two points in pregnancy, prior to 16 weeks gestation and between 20-24 weeks gestation, to measure the presence and level of eight BV-associated bacteria. Women were followed-up for gestational age at delivery via medical records. RESULTS: Among women reporting a prior PTD, women with higher levels of Leptotrichia/Sneathia species, BVAB1 and Mobiluncus spp., prior to 16 weeks gestation, were significantly more likely to experience a SPTD. In addition, pregnant women with a prior PTD and increasing levels of Leptotrichia/Sneathia species (aOR: 9.1, 95% CI 1.9, 42.9), BVAB1 (aOR: 16.4, 95% CI 4.3, 62.7) or Megasphaera phylotype 1 (aOR: 6.2, 95% CI 1.9, 20.6), through 24 weeks gestation, were significantly more likely to experience an SPTD. Among the overall group of pregnant women, the levels of BV-associated bacteria were not related to SPTD. CONCLUSION: Among the group of women reporting a prior PTD, increasing levels of BVAB1, Leptotrichia/Sneathia species, and Megasphaera phylotype 1, through mid-pregnancy were related to an increased risk of SPTD.

Identifying mental health nursing research priorities: A Delphi study.

Abstract Engaging in research and using evidence based practice are essential for mental health nurses to provide quality nursing care to consumers and families. This paper reports on a Delphi study that identified the top 10 mental health nursing research priorities at one area health service in Australia servicing a population of 840,000 people. Initially 390 research questions were identified by nurses and these were then reduced to 56 broader questions. Finally, the top 10 questions were ranked in order of importance. The priority questions were clinically and professionally focussed and included research into the delivery and organisation of mental health services and the need to design and evaluate new practice paradigms for nurses in the primary care setting. The mental health knowledge and skill set of graduates from Australian comprehensive nursing programmes along with improved recruitment and retention of graduates in mental health were also identified priority areas for research.

Gender Diversity in Orthopaedic Surgery Residencies Does Not Translate to Accreditation Council for Graduate Medical Education-Accredited Fellowships.

Introduction: Gender representation among orthopaedic surgery applicants and residents has increased over the past two decades. The aims of this study were to evaluate trends of female fellows in ACGME-accredited orthopaedic subspecialties between 2007 and 2021, and to compare the fellowship trends of female representation to those of ACGME-accredited orthopaedic residencies. Methods: We conducted a retrospective review of publicly available ACGME-accredited fellowship demographic data from 2007 to 2021. The distribution of genders (male vs. female) across subspecialties and orthopaedic surgery residency programs was compared. Chi-square, Spearman correlation, and logistic regression tests were performed to analyze the relationships between year, gender, and fellowship. Results: Chi-square analysis demonstrated a significant relationship between gender and year for orthopaedic residency (p < 0.001), but not for any fellowship. There was a significant negative Spearman correlation between the two variables for hand (r(1844) = -0.06, p = 0.02) and sports medicine (r(2804) = -0.05, p = 0.01) fellowships. The negative Spearman correlation for pediatrics (r(499) = -0.09, p = 0.054) approached but did not reach statistical significance. Logistic regression analysis revealed that, holding year constant and comparing to orthopaedic residency, the odds of male participation increased by 173% (95% CI, 1.8-4.1) in spine, increased by 138% (95% CI, 1.7-3.3) in adult reconstruction, increased by 51% (95% CI, 1.3-1.7) in sports medicine, decreased by 41% (95% CI, 0.5-0.7) in hand, decreased by 36% (95% CI, 0.5-0.9) in foot and ankle, decreased by 48% (95% CI, 0.4-0.7) in musculoskeletal oncology, and decreased by 68% (95% CI, 0.3-0.4) in pediatrics. Conclusion: Although the percentage of female orthopaedic residents in ACGME-accredited programs increased significantly from 2007 to 2021, this has not translated to ACGME-accredited fellowship positions. Future research optimizing methods to improve the representation of females in orthopaedic surgery should be considered. Level of Evidence: III.