The Differential Translation Capabilities of the Human DHFR2 Gene Indicates a Developmental and Tissue-Specific Endogenous Protein of Low Abundance.

A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level.

Buoyant ascent rate profiles for the MK10 and MK11 submarine escape and immersion equipment.

Introduction: Since the U.S. Navy transitioned from the MK10 to the MK11 submarine escape and immersion equipment (SEIE), there has been an increase in the incident rate of pulmonary barotrauma during submarine escape training. This study compares the ascent rate profiles of the MK10 and MK11 SEIE to determine if ascent rate differences between the escape suits are associated with increased pulmonary barotraumas. Methods: Buoyant ascent rates of the MK10 and MK11 SEIE were compared using weighted manikins equivalent to the 1st, 50th, and 99th percentile body weight of a submariner. Human ascents using the MK11 (n=126) were compared to human ascents in the same trainer wearing the MK10 (n=124). Results: Manikin mean ascent times were faster for the MK10 than the MK11 (5.19 seconds vs 5.28 seconds, p ≺ 0.05). Terminal velocity (Vt) was affected by manikin weight (p ≺ 0.001). Human trials confirmed the manikin results. The average mean ascent velocity for the MK10 group was 0.155 meters/ second faster than the MK11 group's mean ascent velocity (p ≺ 0.001). Mean ascent velocity was inversely correlated with all anthropometrics for the MK10 group (p ≺ 0.01). Neither height nor body mass index showed a significant association with mean ascent velocity for the MK11 group. Conclusions: The Vt of buoyant ascents is significantly affected by body weight. As the mean ascent rate of the MK11 is slower than that of the MK10, ascent rate profile differences between the suits do not appear to explain the recent increase in pulmonary barotrauma incident rates during escape training.

A Preliminary Description of the Health of Women Navy Divers: An Examination of Linked Medical, Personnel, and Dive Log Data for 47 Women Divers Who Separated Between 2008 and 2018.

INTRODUCTION: Although women have always served in the U.S. Armed Forces, it has only been in the last half century that systematic examinations have been done on the health issues experienced by military women. Still, little is known about how occupational health risks among Navy divers might vary between men and women. Our objective was to use available data to examine health issues among all separating divers and then determine how prevalence rates varied between men and women for diagnoses made within the diver's last year of active duty service. MATERIALS AND METHODS: For this retrospective observational study, medical records and personnel data were linked with dive logs at the individual level. We calculated sex-specific prevalence rates and relative risks per 1,000 divers by major diagnostic categories and by specific disease diagnoses. RESULTS: We identified 47 women among the 4,623 active duty Navy divers (1.0%) who separated between 2008 and 2018. Ages varied between 19 and 54 years (M = 33, SD = 8) for women, compared to men who were 18-65 years (M = 35, SD = 9). When compared to men, women had about six times the rate of diseases of the genitourinary system, twice the rate of respiratory system diseases, and about four times as many diagnoses of disorders of the lacrimal system. CONCLUSIONS: The findings of much higher relative risks for women for conditions such as genitourinary disease, skin conditions, and acute respiratory infections require follow-up research to look for causes and potential risk reduction interventions. Future research must determine specific and relative risks as a necessary precursor to developing, implementing, and testing potentially sex-specific risk reduction and health improvement interventions.

Prescription medication use and trends for U.S. Navy submariners from 2007 to 2018.

Introduction: This is the first study to examine population medication prescription rates among U.S. submariners by common therapeutic classifications. Methods: Individual-level pharmacy records during the years 2007 to 2018 were extracted from the Military Health System's Pharmacy Data Transaction Service (PDTS) file. Demographic and military factors captured from Navy personnel files were linked to PDTS records. Logistic regression models were used to identify characteristics and trends associated with prevalence. Published total rates for other active-duty components were compared to submariner rates. Results: There were data for 50,720 submariners, among whom 576,782 prescriptions were filled. Prevalence rates decreased significantly from 2007-2018 among most drug classes. Central nervous system agents accounted for 31% of the total prescriptions, followed by 12% for eye, ear, nose, and throat preparations, and 10% for anti-infective agents. Higher prescription rates were associated with being enlisted, younger, a woman, lower-ranked, or Hispanic. The mean yearly prescription rate was 2.7 per submariner, less than half of the overall rate of all military components. Conclusion: The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.

Health Conditions Among Navy Submariners at the End of Active Duty; A Retrospective Cohort Study.

INTRODUCTION: Maintaining healthy, well-trained, and highly qualified armed forces is critical for ensuring military readiness. The purpose of this article is to contribute to the body of research focused on the health of U.S. Navy submariners and to identify the health conditions of U.S. Navy submariners during their final year of active duty service. MATERIALS AND METHODS: In this retrospective cohort study, we examined medical records and personnel files of separating U.S. Navy sailors who were: (1) active duty between 2009 and 2018; (2) separated before 2019; and (3) were assigned to a submarine for at least 30 days. Both officers and enlisted service members were included. We linked, described, and analyzed data from the Defense Health Agency, Military Health System Data Repository (MDR), and the Bureau of Naval Personnel (BUPERS). International Classification of Diseases (ICD) diagnoses codes were obtained from MDR. Data collected from BUPERS include age, sex, and rank. We determined the number of individuals who had at least one diagnosed condition (identified as a three-digit ICD code). We report the number of diagnoses and calculate prevalence rates and confidence intervals per condition, as well as prevalence rates per year, using standard formulas. The study was approved by the Naval Submarine Medical Research Laboratory Institutional Review Board. RESULTS: During the study period, 26,014 submariners separated from the Navy. The average number of separations per year was 2,601. About a third of the separating submariners were in the 25 to 29 age group and over 50% were under 30 years of age. Of the three-digit individual ICD codes, some of the highest operationally relevant rates over the 10-year study period (2009-2018) were for joint disorders (prevalence rate [PR] = 180 per 1,000 submariners), back disorders (PR = 128), and sleep disorders (PR = 134). Three mental-health-related conditions were also among the 20 conditions with the highest rates. CONCLUSIONS: High rates of specific diagnoses such as joint disorders indicate the need for additional study to examine causal relationships, to determine which conditions may contribute to lost work time, early separations, or low rates of reenlistment and which conditions might be a result of specific military occupations or duties. Study strengths are the large number of subjects and the long period of observations. A study weakness was the inability to identify submariners who separated because of health conditions. The overall impact of the study is that it identifies urgent health risks and establishes a way to prioritize future research. Future research should include a focus on medically separated personnel; compare rates for submariners to other military groups including all-Navy and all-Department of Defense; and determine specific and relative risks as a necessary precursor to developing, implementing, and testing risk reduction and health improvement interventions.

Health conditions among Navy divers at end of service: a retrospective cohort study.

PURPOSE: To identify the most prevalent health conditions among divers during their last year of Navy service. METHODS: For this retrospective descriptive study we used data from the Dive Jump Reporting System to identify 4,623 active-duty divers who separated between 2008 and 2018. Medical records, dive histories, and personnel files were merged, linked and analyzed at the individual level. RESULTS: On average, 420 divers separated each year. Among the separating divers, 99% were male, 26% were aged 25 to 29 years old with a mean age of 35 (SD = 9, range 18 to 65). The major medical categories with the highest numbers of divers affected were: musculoskeletal system diseases (prevalence rate (PR) = 515.2 per 1,000 divers/year); nervous system (PR = 411.9); injury and poisonings (PR = 249.8); and mental disorders (PR = 237.3). Of the 50 specific conditions that affected the most divers the top four were joint disorders (PR = 34.5), disorders of refraction and accommodation (PR = 30.1), back disorders (PR = 26.8) and organic sleep disorders (PR = 21.6). Compared to divers with fewer than 29 dives, divers with 49-plus dives were about twice as likely to have diagnoses related to symptoms involving head and neck. CONCLUSIONS: The study found high rates of conditions such as musculoskeletal disorders, joint and back disorders, and some mental health related disorders. Special warfare divers have high rates of hearing loss, and other disorders of ear. The results show the need and to develop and implement group-specific mitigation programs.

The Effect of Using an Active Earmuff on High Frequency Hearing in United States Marine Corps Weapons Instructors.

OBJECTIVES: To investigate the change in hearing and perceived comfort over 1 year related to using an active hearing protection device (HPD) among United States Marine Corps (USMC) personnel routinely exposed to hazardous noise. METHODS: USMC Weapons Instructors (n = 127) were issued an active earmuff that met military standards and was compatible with other protective equipment. These participants completed pre- and post-hearing tests and comfort surveys. A control cohort (n = 94) was also included to compare individual changes in high-frequency pure tone average (HF-PTA) over 1 year. RESULTS: The control group's HF-PTA was 3 dB worse than the intervention group after only 1 year. Survey responses revealed perceived improvements in the ability to hear and understand, situational awareness, and safety. CONCLUSIONS: Active HPDs can reduce hearing loss and improve hearing-related occupational tasks.

Patient Safety: We've Come a Long Way.

Patient safety has come a long way since the release of the 1999 Institute of Medicine report To Err Is Human. This report revealed the immense size of the problem of preventable adverse events - events that in the past we assumed were "just complications" occurring in the normal course of diagnosis and treatment. Simultaneously, shining the light on patient safety "took the lid off quality." Those of us involved in healthcare provision always had a commitment to providing high-quality care, yet the focus of many key stakeholders on the importance of high-quality healthcare had been limited. The focus tended to be disproportionately on the rising cost of healthcare rather than a balanced focus on quality. Now, we respect the imperative of achieving high-quality healthcare.

Patient Safety: Patient Involvement Matters.

As the co-chair of Patients for Patient Safety Canada (PFPSC), I have had the opportunity to be a guest editor for this Special Issue of Healthcare Quarterly and, consequently, have reviewed and critiqued each article. I also was a patient partner in the National Patient Safety Consortium, the work of which is the basis for the articles in this issue. Patient safety is a serious issue in Canada. In fact, unintended harm while receiving healthcare is the third leading cause of death in Canada (RiskAnalytica 2017). The papers in this issue describe initiatives that have the potential to and/or have contributed to reducing patient harm if implemented across our system and in such a way that patients and families are an integral part of the process.

Medication-enhanced behavior therapy for alcohol use disorder: Naltrexone, Alcoholics Anonymous Facilitation, and OPRM1 genetic variation.

Medication-assisted behavior treatment for alcohol use disorder (AUD) holds promise to enhance the efficacy of medication and of behavior therapy when administered individually. The present study examines the treatment benefit of combined outpatient naltrexone (NTX) treatment with Alcoholics Anonymous Facilitation (AAF) behavior therapy, in the context of OPRM1 genotype. The minor OPRM1 Asp40 G-allele has been associated with greater positive reinforcing effects of alcohol consumption and greater alcohol craving, suggesting that individuals carrying the OPRM1 G allele may have an improved naltrexone response. Twenty patients, including 7 G-allele carriers, received 90 days of naltrexone with medication support and dispensing sessions, and ten AAF behavior therapy sessions. During treatment and the eight-week posttreatment follow-up, an overall increase in percent days abstinent was observed for the sample as a whole, but G-allele carriers reported relatively heavier drinking relative to other subjects. These findings suggest that this enhanced medication-assisted behavior treatment is a promising therapeutic combination, and mirror other recent findings that G-allele carriers may require more intensive treatment.

Identifying Predictors of Pressurized Submarine Escape Training (PSET) Attrition.

Pressurized Submarine Escape Training (PSET) physically prepares submariners to safely escape a submarine at depth. Failure to complete PSET is not a submarine service disqualification. Serious medical incidents are rare, but the safety record tradeoff has been low throughput. From 2009 to 2015, only 34% of students screened completed PSET. Students may be medically screened out of the training altogether (disqualified), or dropout during the physical training (attrite). Training records from 12,122 U.S. Navy students were used to identify factors contributing to training disqualification and attrition. Multivariate logistic regression model predictors included demographic and screening items. Association to PSET disqualification included cold/congestion/cough (ORadj 12.34), limited duty status (ORadj 4.29), Physical Readiness Test failure (ORadj 3.37), pneumonia or bronchitis in last 2 years (ORadj 3.17) and nervousness or anxiety in tight spaces (ORadj 2.37). Basic Enlisted Submarine School students were more likely to be disqualified and attrite than other submariner groups, and black/African American (ORadj 1.53) students were more likely to attrite than white students. Only cold/congestion/cough (ORadj 1.52), trouble swimming (ORadj 1.53), and screening during cold/flu season (ORadj 1.28), were associated with training attrition. Recommendations to modify screening requirements are listed in conclusions.

Safe and effective person- and family-centered care practices during transitions from hospital to home-A web-based Delphi technique.

BACKGROUND: Research has shown that adverse events during care transitions from hospital to home can have a significant impact on patients' outcomes, leading to readmission, delayed healing or even death. Gaps exist in the ways of monitoring care during transition periods and there is a need to help organizations better implement and monitor safe person-and family-centered care. Value statements are a way to obtain narratives in lay terms about how well care, treatment and support is organized to meet the needs and preferences of patients/families. The purpose of this study was to identify the value statements that are perceived by decision-makers and patients/families to best signify safe person- and family-centered care during transitions from hospital to home. METHODS: Between January and September 2017, a web-based Delphi was used to survey key stakeholders in acute care and home care organizations across Canada. RESULTS: Decision-makers (n = 22) and patients/families (n = 24) from five provinces participated in the Delphi. Following Round 1, 45 perceived value statements were identified. In Round 2, consensus was received on 33/45 (73.3%) by decision-makers, and 30/45 (66.7%) by patients/families. In Round 3, additional value statements reached consensus in the decision-makers' survey (3) and in the patients/families' survey (2). A total of 30 high priority value statements achieved consensus derived from both the decision-makers' and patients/families' perspectives. CONCLUSION: This study was an important first step in identifying key consensus-based priority value statements for monitoring care transitions from the perspective of both decision-makers and patients/families. Future research is needed to test their usability and to determine whether these value statements are actually suggestive of safe person-and family-centered care transition interventions from hospital to home.

Nursing and Dental Students' Reflections on Interprofessional Practice After a Service-Learning Experience in Appalachia.

Nowhere is the discrepancy between good and poor oral health status more pronounced in the U.S. than in the Appalachian region, where there is a high incidence of dental problems related to non-flouridated water, limited access to care, and tooth loss. To address these disparities, in 2016 University at Buffalo dental and nurse practitioner faculty members led a group of dental and nursing students on a two-day service-learning experience in rural Tennessee. The aim of this study was to assess the dental and nursing students' reflections on this interprofessional service-learning experience in Appalachia. After the program, all 36 students who took part in it were invited to complete a survey with open-ended questions about the experience and their attitudes about interprofessional practice. Of the students, 34 (94.4%) returned the surveys, and 23 completed all the questions. Thematic analysis was used to code and analyze the student comments, which were then organized into themes. Five themes emerged: facilitating care through teamwork, gaining mutual respect, gaining confidence, understanding dental role in overall health, and relieving suffering. The overarching pattern was the link among all the themes: that everyone has a part to play in ensuring that patients get the best care. The themes and overarching pattern corresponded to the Interprofessional Education Collaboration (IPEC) competencies and the overall goal of delivering patient-centered care to a population that is underserved. These findings suggest that exposure to patients who lack dental care and have severe oral health problems can impact developing nursing and dental professionals in ways that can increase their appreciation of interprofessional practice and their future willingness to provide care in underserved settings.

Patients as Front-Line Owners and Partners in Improving Quality and Safety.

As patient partners, we are pleased by the success of the front-line ownership (FLO) approach in advancing safe care in a variety of initiatives and settings. The FLO underlying principles and approach deeply resonate with us as illustrated in the following quotes from the paper: "Nothing about me without me," "Most passionate change agents are not in roles that typically get invited to participate," "Inviting anybody who is interested in the problem at hand," "FLO creates a way to break down hierarchies, increase positive dialogue between diverse players in organizations, and encourage people who may not have felt empowered previously to come forward and problem-solve." It is not described in the article if and how patients and/or patient partners were involved; therefore, we call on the authors to follow up with that information because it can provide valuable lessons to others who will be looking at implementing FLO in their organizations. Based on our decade-long experience as patient partners at all system levels, on literature and leading practices (key references included) we argue that patients have an important role to play in improvement initiatives and recommend partnering with patients in all improvement efforts.

Identification and Treatment of Adolescents With Perinatal Anxiety and Depression.

Perinatal mood and anxiety disorders (PMAD) are the most common, yet under-diagnosed and undertreated complication of pregnancy, affecting up to 50% of pregnant and parenting teens. PMAD are a global health issue that can have devastating effects on the mental, physical, emotional, developmental health, and social life of the mother, infant, and family. Adolescents present with similar symptoms of PMAD as their adult counterparts, but also experience isolation from their peer group and lack of resources and coping strategies, as well as difficulty sleeping and lack of concentration and ability to focus. Nurses and nurse practitioners are in an ideal position to assess preexisting risk factors for PMAD. The current applied evidence-based article addresses the diagnosis of PMAD, provides a conceptual framework for understanding the intra- and interpersonal dynamics affecting teens with PMAD, and suggests a new screening tool to guide diagnosis. An easy to recall mnemonic for diagnosis and referral (SAIL AHEAD) is proposed. By using the SAIL AHEAD mnemonic, providers will impact adolescents' parenting success and resiliency, thereby enhancing their future success in life. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 23-29.].

Nurse Practitioners' Education, Awareness, and Therapeutic Approaches for the Management of Fibromyalgia.

BACKGROUND: In the United States, fibromyalgia affects 2%-5% of the adult population, rendering it the most common chronic, widespread pain condition. The American College of Rheumatology has published diagnostic criteria for fibromyalgia, with the latest version in 2010. PURPOSE: The purpose of this study was to evaluate nurse practitioners' education and awareness of fibromyalgia and to evaluate nurse practitioners' practices for the management of fibromyalgia. METHODS: Sixty-six nurse practitioners voluntarily completed an online survey regarding their education, diagnosis, and treatment options for patients with fibromyalgia. RESULTS: The majority of participants reported that they always or occasionally had difficulty diagnosing fibromyalgia and worried about labeling their patients as having fibromyalgia. The most commonly used agents were nonsteroidal anti-inflammatory drugs (70%), serotonin norepinephrine reuptake inhibitors (61%), selective serotonin reuptake inhibitors (51%), and muscle relaxants (44%). Nondrug therapies included exercise (88%), cognitive behavior therapy (58%), and nutrition (56%). CONCLUSION: Further education is needed for nurse practitioners to increase confidence in diagnosing and managing fibromyalgia.

Comparison of Body Composition Assessed by Dual-Energy X-Ray Absorptiometry and BMI in Current and Former U.S. Navy Service Members.

BACKGROUND: Little is known of the diagnostic accuracy of BMI in classifying obesity in active duty military personnel and those that previously served. Thus, the primary objectives were to determine the relationship between lean and fat mass, and body fat percentage (BF%) with BMI, and assess the agreement between BMI and BF% in defining obesity. METHODS: Body composition was measured by dual-energy X-ray absorptiometry in 462 males (20-91 years old) who currently or previously served in the U.S. Navy. A BMI of ≥ 30 kg/m2 and a BF% ≥ 25% were used for obesity classification. RESULTS: The mean BMI (± SD) and BF% were 28.8 ± 4.1 and 28.9 ± 6.6%, respectively, with BF% increasing with age. Lean mass, fat mass, and BF% were significantly correlated with BMI for all age groups. The exact agreement of obesity defined by BMI and BF% was fair (61%), however, 38% were misclassified by a BMI cut-off of 30 when obesity was defined by BF%. CONCLUSIONS: From this data we determined that there is a good correlation between body composition and BMI, and fair agreement between BMI and BF% in classifying obesity in a group of current and former U.S. Navy service members. However, as observed in the general population, a significant proportion of individuals with excess fat are misclassified by BMI cutoffs.

Factorial Validity of the Decisional Involvement Scale as a Measure of Content and Context of Nursing Practice.

Decisional involvement is widely recognized as an essential component of a professional nursing practice environment. In recent years, researchers have added to the conceptualization of nurses' role in decision-making to differentiate between the content and context of nursing practice. Yet, instruments that clearly distinguish between these two dimensions of practice are lacking. The purpose of this study was to examine the factorial validity of the Decisional Involvement Scale (DIS) as a measure of both the content and context of nursing practice. This secondary analysis was conducted using data from a longitudinal action research project to improve the quality of nursing practice and patient care in six hospitals (N = 1,034) in medically underserved counties of Pennsylvania. A cross-sectional analysis of baseline data from the parent study was used to compare the factor structure of two models (one nested within the other) using confirmatory factor analysis. Although a comparison of the two models indicated that the addition of second-order factors for the content and context of nursing practice improved model fit, neither model provided optimal fit to the data. Additional model-generating research is needed to develop the DIS as a valid measure of decisional involvement for both the content and context of nursing practice.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders.

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.