Load carriage exercise increases calcium absorption and retention in healthy young women.

Aerobic exercise reduces circulating ionized Ca (iCa) and increases parathyroid hormone (PTH), but the cause and consequences on Ca handling are unknown. The objective of this study was to determine the effects of strenuous exercise on Ca kinetics using dual stable Ca isotopes. Twenty-one healthy women (26.4 ± 6.7 yr) completed a randomized, crossover study entailing two 6-d iterations consisting of either 60 min of treadmill walking at 65% VO2max wearing a vest weighing 30% body weight on study days 1, 3, and 5 (exercise [EX]), or a rest iteration (rest [REST]). On day 1, participants received intravenous 42Ca and oral 44Ca. Isotope ratios were determined by thermal ionization mass spectrometry. Kinetic modeling determined fractional Ca absorption (FCA), Ca deposition (Vo+), resorption (Vo-) from bone, and balance (Vbal). Circulating PTH and iCa were measured before, during, and after each exercise/rest session. Data were analyzed by paired t-test or linear mixed models using SPSS. iCa decreased and PTH increased (P < .001) during each EX session and were unchanged during REST. On day 1, urinary Ca was lower in the EX pool (25 ± 11 mg) compared to REST (38 ± 16 mg, P = .001), but did not differ over the full 24-h collection (P > .05). FCA was greater during EX (26.6 ± 8.1%) compared to REST (23.9 ± 8.3%, P < .05). Vbal was less negative during EX (-61.3 ± 111 mg) vs REST (-108 ± 23.5 mg, P < .05), but VO+ (574 ± 241 vs 583 ± 260 mg) and VO- (-636 ± 243 vs -692 ± 252 mg) were not different (P > .05). The rapid reduction in circulating iCa may be due to a change in the miscible Ca pool, resulting in increased PTH and changes in intestinal absorption and renal Ca handling that support a more positive Ca balance.

Development of a Database for the Estimation of Heme Iron and Nonheme Iron Content of Animal-Based Foods.

Background: Total iron (TI) intake and differentiation between heme iron (HI) and nonheme iron (NHI) are uncommon despite markedly different bioavailability. Objectives: To create a database compiling information from studies that directly assessed the HI content of animal products using the Hornsey method, and to explore differences in estimates of HI intake between the data compiled and the Monsen method. Methods: A literature search identified studies that chemically characterized the HI content of animal-based foods using the Hornsey method; HI, NHI, and TI contents (mg/100 g) were compiled. Information was grouped by animal type and cooking method, and mean (± SD) HI% was calculated. Using a 24-h dietary record, differences in HI and NHI intake using the compiled information and the Monsen approach were explored. Results: Actual HI% values ranged from 7% to 94%. Raw foods had the highest HI% [raw duck (94% ± 4%), raw blood curd (82% ± 4%), and raw beef (79% ± 9%)]. Boiled foods had the lowest HI% [boiled shrimp (11% ± 5%) and meatballs (15% ± 6%)]. Cooked foods with the highest HI% were beef (70% ± 10%) and lamb (70% ± 9%). In many instances, applying actual HI% from the complied database produced markedly different measures of the HI content of foods [cooked beef (Monsen: 1.3 mg/100 g); (Hornsey: 2.3 mg/100 g)]. Estimation of iron intake in a 24-h recall demonstrated that using animal-specific HI% results in different estimates of HI intake [Monsen: 1.2 mg HI (40%); Hornsey: 1.8 mg HI (59%)]. Conclusions: Animal-based foods have variable HI%. A fixed HI:NHI ratio does not reflect this variation and could give rise to inaccurate estimates of HI content in food and HI intake. Consideration of this variation in HI% may improve our ability to link dietary intake with iron status and important health outcomes.

Associations between genetically predicted iron status and cardiovascular disease risk: A Mendelian randomization study.

Background: Mendelian randomization (MR) studies suggest a causal effect of iron (Fe) status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables (IV) on CVD risk factors. We aimed to investigate the effect of Fe status on CVD risk controlling for CVD risk factors. Methods: Fe biomarker IVs (total Fe binding capacity (TIBC, n=208,422), transferrin saturation (TSAT, n=198,516), serum Fe (SI, n=236,612), ferritin (n=257,953)) were selected from a European GWAS meta-analysis. We performed two-sample univariate (UV) MR of each Fe trait on CVD outcomes (all-cause ischemic stroke (IS), cardioembolic IS (CES), large artery IS (LAS), small vessel IS (SVS), and coronary heart disease (CHD)) from MEGASTROKE (n=440,328) and CARDIoGRAMplusC4D (n=183,305). We then implemented multivariate (MV) MR conditioning on six CVD risk factors from independent European samples to evaluate their potential confounding and/or mediating effects on the observed Fe-CVD associations. Results: With UVMR analyses, we found higher genetically predicted Fe status to be associated with a greater risk of CES (TSAT: OR 1.17 [95%CI 1.03, 1.33], SI: OR 1.21 [ 95%CI 1.02, 1.44]; TIBC: OR 0.81 [95%CI 0.69, 0.94]). The detrimental effects of Fe status on CES risk remained unaffected when adjusting for CVD risk factors (all P<0.05). Additionally, we found diastolic blood pressure (DBP) to mediate between 7.1-8.8% of the total effect of Fe status on CES incidence. While UVMR initially suggested a protective effect of Fe status on LAS and CHD, MVMR analyses factoring CVD risk factors revealed a complete annulment of this perceived protective effect (all P>0.05). Discussion: Higher Fe status was associated with a greater risk of CES independent of CVD risk factors, and this effect was partly mediated by DBP. These findings support a role of Fe status as a modifiable risk factor for CES.

Placental ferroportin protein abundance is associated with neonatal erythropoietic activity and iron status in newborns at high risk for iron deficiency and anemia.

BACKGROUND: Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. OBJECTIVES: This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. METHODS: Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). RESULTS: FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: ß: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: ß: 0.20; 95% CI: 0.03, 0.18; hepcidin: ß: -0.06; 95% CI: -0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (ß-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (ß: -0.02; 95% CI: -0.03, -0.003), EPO (ß: 0.07; 95% CI: 0.01, 0.14), and sTfR (ß: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (ß: 0.08, 95% CI: 0.02, 0.14), TBI (ß: 0.02; 95% CI: 0.009, 0.04), EPO (ß: -0.10; 95% CI: -0.19, -0.01), sTfR (ß: -0.16: 95% CI: -0.27, -0.06), and hepcidin (ß: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). CONCLUSIONS: Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.

Coworker support amplifies strain in the COVID-19 pandemic for working parents.

The COVID-19 pandemic directly threatened our health and safety, while contradictory scientific and media reports generated uncertainty. Social information processing theory suggests that employees may have relied on their coworkers, via coworker support, to make sense of the confusion. Because previous research shows that coworker support can counterintuitively increase strain, we investigated the effects of coworker support on strain during the pandemic. Specifically, we collected data from a heterogeneous US sample of 314 working parents in May 2020 to illustrate the path from personal traits (i.e., optimism, generalized self-efficacy, and internal locus of control) to COVID-19 anxiety to workplace outcomes (i.e., self-rated performance, emotional exhaustion, and work-family conflict) in a multiphasic study design. Employees with low levels of these traits reported more COVID-19 anxiety, and in turn, more decrement to their workplace outcomes. This mediation is moderated by coworker social support, such that the indirect effect is exacerbated by coworker social support. This is consistent with social information processing theory, which states that coworker social support can unintentionally corroborate and amplify employee stress perceptions. We therefore recommend that, when faced with significant adversity, organizations provide communication training oriented toward increasing positive coworker interactions and guiding social information.

The Efficacy of a Mental Skills Training Course for Collegiate Athletes.

CONTEXT: Psychological skills training improves performance in athletes. However, few studies have looked at the efficacy and satisfaction of mental skills training programs for collegiate athletes. OBJECTIVE: We aimed to evaluate satisfaction of collegiate athletes with a 6-session mental skills course, and to assess changes in mental toughness and coping skills before and after the course. DESIGN: Prospective cohort study following collegiate female athletes through a 6-session mental skills course. SETTING: Division 1 collegiate athletic teams. PATIENTS/PARTICIPANTS: 54 Division I female athletes (mean age =19.8) participated in the program and 42 (77.7 %) completed pre-course assessments, which subsequent evaluations were matched to. MAIN OUTCOME MEASURES: The Athletic Coping Skills Inventory (ACSI, range=0-84) and Mental Toughness Index (MTI, range=8-56) assessed coping skills and mental toughness pre-course, immediate post-course and 4-month post course. Satisfaction was assessed on a 10-point scale. RESULTS: For participants with paired pre- and immediate post-course data (n=37, 68.5%), MTI scores improved by a mean 2.6 points (95% CI=1.1-4.1; p=0.001) and ACSI scores improved by a mean 4.0 points (95% CI=0.6-7.4; p=0.02). At four-month follow-up (n=25, 46.2%), no change was detected from pre-course in mean MTI score (p=0.72), but there was a significant increase of 3.4 points in mean ACSI (95% CI=0.4-6.4; p=0.03). Overall satisfaction had a median score of 9/10 (IQR, 8-10) at post-course, and eighteen participants (48.6%) shared positive free-text comments regarding course delivery, content, and impact. No negative feedback was reported. CONCLUSIONS: Mental toughness and coping skills scores significantly improved at post-course assessment, with coping skills scores maintaining their effect at four months. The improvements identified spark the question of the potential impact of mental skills training programs when studied in larger athlete populations or over more sustained periods of time. Athletes reported being highly satisfied with course content and reported overall positive experiences.

Skills to Enhance Positivity in adolescents at risk for suicide: Protocol for a randomized controlled trial.

BACKGROUND: Suicide and suicidal behavior during adolescence have been steadily increasing over the past two decades. The preponderance of interventions focuses on crisis intervention, underlying psychiatric disorders, regulating negative affect, and reducing cognitive distortions. However, low positive affectivity may be a mechanism that contributes to adolescent suicidal ideation and behaviors independent of other risk factors. Skills to Enhance Positivity (STEP) is an acceptance-based intervention, designed to increase attention to, and awareness of, positive affect and positive experiences. Results from a pilot RCT demonstrated engagement of the target (positive affect) and a decrease in clinical outcomes (suicidal events; i.e., either a suicide attempt or an emergency intervention for an acute suicidal crisis), providing support to test the clinical effectiveness of STEP in a larger clinical trial with clinical staff implementing the intervention. OBJECTIVE: To test the effectiveness of STEP, compared to Enhanced Treatment as Usual (ETAU), in reducing suicidal events and ideation in adolescents admitted to inpatient psychiatric care due to suicide risk. We hypothesize that those randomized to STEP, compared to ETAU, will have lower rates of suicide events, active suicidal ideation (SI), and depressed mood over the 6-month follow-up period. We hypothesize that those randomized to STEP, compared to ETAU, will demonstrate greater improvement in the hypothesized mechanisms of attention to positive affect stimuli and gratitude and satisfaction with life. METHODS: Participants will be randomized to either STEP or ETAU. STEP consists of four in-person sessions focused on psychoeducation regarding positive and negative affect, mindfulness meditation, gratitude, and savoring. Mood monitoring prompts and skill reminders will be sent via text messaging daily for the first month post-discharge and every other day for the following two months. The ETAU condition will receive text-delivered reminders to use a safety plan provided at discharge from the hospital and healthy habits messages, matched in frequency to the STEP group. This trial was registered on 6 August 2021 (ClinicalTrials.gov NCT04994873). RESULTS: The STEP protocol was approved by the National Institute of Mental Health (NIMH) Data and Safety Monitoring Board on March 4, 2022. The RCT is currently in progress. DISCUSSION: The STEP protocol is an innovative, adjunctive treatment that has the potential to have positive effects on adolescent suicidal ideation and attempts beyond that found for standard treatment alone.

The Placenta: A Maternofetal Interface.

The placenta is the gatekeeper between the mother and the fetus. Over the first trimester of pregnancy, the fetus is nourished by uterine gland secretions in a process known as histiotrophic nutrition. During the second trimester of pregnancy, placentation has evolved to the point at which nutrients are delivered to the placenta via maternal blood (hemotrophic nutrition). Over gestation, the placenta must adapt to these variable nutrient supplies, to alterations in maternal physiology and blood flow, and to dynamic changes in fetal growth rates. Numerous questions remain about the mechanisms used to transport nutrients to the fetus and the maternal and fetal determinants of this process. Growing data highlight the ability of the placenta to regulate this process. As new technologies and omics approaches are utilized to study this maternofetal interface, greater insight into this unique organ and its impact on fetal development and long-term health has been obtained.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study.

BACKGROUND: Developmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts. OBJECTIVES: This study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex. METHODS: The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models. RESULTS: The risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 µg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males. CONCLUSIONS: Relationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals.

Hemoglobin distributions and prevalence of anemia in a multiethnic United States pregnant population.

BACKGROUND: Few normative longitudinal hemoglobin data are available to estimate the prevalence and risk factors for anemia among a multiethnic United States pregnant population. OBJECTIVES: The aim of this study was to characterize hemoglobin distributions and prevalence of anemia in a pregnant population receiving care at a large urban medical center. METHODS: A retrospective medical chart review was undertaken in 41,226 uncomplicated pregnancies of 30,603 pregnant individuals who received prenatal care between 2011 and 2020. Mean hemoglobin concentrations and anemia prevalence in each trimester and incidence of anemia during pregnancy in a subset of 4821 women with data in each trimester were evaluated in relation to self-reported race and ethnicity and other possible risk factors. Risk ratios (RRs) of anemia were determined using generalized linear mixed-effects models. Smoothed curves describing changes in hemoglobin across pregnancy were created using generalized additive models. RESULTS: The overall prevalence of anemia was 26.7%. The observed fifth percentiles of the hemoglobin distributions were significantly lower than the United States CDC anemia cutoffs in the second and third trimesters (T3). The RR (95% CI) of anemia were 3.23 (3.03, 3.45), 6.18 (5.09, 7.52), and 2.59 (2.48, 2.70) times higher in Black women than that in White women in each trimester, respectively. Asian women recorded the lowest risk of anemia compared with other racial groups in T3 (compared with White womenRR: 0.84; 95% CI: 0.74, 0.96). Hispanic women presented a higher risk of anemia in T3 than non-Hispanic women (RR: 1.36; 95% CI: 1.28, 1.45). In addition, adolescents, individuals with higher parity, and those carrying multiple fetuses experienced a higher risk of developing anemia in late gestation. CONCLUSIONS: Anemia was evident in more than one-quarter of a multiethnic United States pregnant population despite current universal prenatal iron supplementation recommendations. Prevalence of anemia was higher among Black women and lowest among Asian and White women.

Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples.

BACKGROUND: The iron regulatory hormones erythroferrone (ERFE), erythropoietin (EPO), and hepcidin, and the cargo receptor nuclear receptor coactivator 4 (NCOA4) are expressed in the placenta. However, determinants of placental expression of these proteins and their associations with maternal or neonatal iron status are unknown. OBJECTIVES: To characterize expression of placental ERFE, EPO, and NCOA4 mRNA in placentae from newborns at increased risk of iron deficiency and to evaluate these in relation to maternal and neonatal iron status and regulatory hormones. METHODS: Placentae were collected from 114 neonates born to adolescents carrying singletons (14-18 y) and 110 neonates born to 54 adults (20-46 y) carrying multiples. Placental EPO, ERFE, and NCOA4 mRNA expression were measured by RT-qPCR and compared with maternal and neonatal iron status indicators (SF, sTfR, total body iron, serum iron) and hormones. RESULTS: Placental ERFE, EPO, and NCOA4 mRNA were detected in all placentae delivered between 25 and 42 wk of gestation. Relationships between placental ERFE and EPO differed by cohort. In the multiples cohort, placental EPO and ERFE were positively correlated (P = 0.004), but only a positive trend (P = 0.08) was evident in the adolescents. Placental EPO and ERFE were not associated with maternal or neonatal iron status markers or hormones in either cohort. Placental NCOA4 was not associated with placental EPO or ERFE in either cohort but was negatively associated with maternal SF (P = 0.03) in the multiples cohort and positively associated with neonatal sTfR (P = 0.009) in the adolescents. CONCLUSIONS: The human placenta expresses ERFE, EPO, and NCOA4 mRNA as early as 25 wk of gestation. Placental expression of ERFE and EPO transcripts was not associated with maternal or neonatal iron status. Greater placental NCOA4 transcript expression was evident in women and newborns with poor iron status (lower SF and higher sTfR, respectively). Further research is needed to characterize the roles of these proteins in the human placenta. TRIAL REGISTRATION NUMBER: These clinical trials were registered at clinicaltrials.gov as NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902) and NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802).

Experiences of Inpatient Psychiatric Nursing Care among People Who Have Survived a Suicide Attempt.

Nurses are front line providers for people who have been hospitalized following a suicide attempt, yet few studies have explored this population's experiences specifically with nursing care in inpatient psychiatric units. The purpose of this study was to hear directly from people who have survived a suicide attempt about their experiences with inpatient psychiatric nursing care following a suicide attempt in order to identify strengths and weaknesses of current practices and elicit suggested improvements. Qualitative in-depth interviews were conducted with people who were previously psychiatrically hospitalized following a suicide attempt (N = 9; Mage=42). Applied thematic analysis was used to identify themes related to positive and negative experiences with nursing care during hospitalization and advice for nurses. Findings demonstrated that positive experiences with nurses related to empathy, friendliness, feeling supported, flexibility, and active listening, while negative experiences centered around feeling stigmatized, invalidated, degraded, and coerced. Advice for nurses included being self-aware of preconceived or stigmatized notions, practicing empathy, listening, and humanity. The results of this study indicate the need for compassionate care, training to reduce nurse stigma, and adequate resources for nurses to mitigate emotional strain and burnout.

Examining Racial/Ethnic Differences in the Association of Victimization and Suicidal Thoughts and Behaviors with Alcohol Use Among Sexual Minority Youth.

Purpose: Integrating Minority Stress Theory and Bagge and Sher's Theoretical Framework of the Alcohol-Suicide Attempt Relation, this study aimed to test whether experiencing both minority stress and suicidal thoughts and behaviors (STBs) had a greater strength of association with Latinx and Black sexual minority youth (SMY)'s alcohol use compared with that of White SMY. Methods: Using data on 2341 non-Latinx Black, Latinx, and non-Latinx White SMY from the 2015 and 2017 Youth Risk Behavior Surveys, we tested the prevalence of STBs, victimization, and alcohol use for Black and Latinx participants compared with White participants. Multivariate logistic regression analyses tested the main effects of STBs, victimization, and race/ethnicity on alcohol use. Finally, interaction terms assessed the interaction among STBs, victimization, and race/ethnicity on alcohol use. Results: The results supported our hypothesis, based on Minority Stress Theory, that experiencing victimization would be associated with greater alcohol use. Results also supported Bagge and Sher's theoretical framework showing that suicide plan and attempts were associated with greater alcohol use. When taking all of these stressors into account, results showed that Latinx SMY who experienced victimization had greater current prevalence of alcohol use than their White counterparts. However, Latinx SMY who were victimized and experienced suicidal ideation reported lower alcohol use than White SMY. Conclusion: These findings support the double jeopardy and resiliency hypotheses, which suggest that minority stressors have differing associations for each racial/ethnic SMY group's alcohol use. More research is needed that helps to disentangle the protective and risk factors for alcohol use among Black and Latinx SMY.

Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes.

High levels of the inflammatory cytokine IL-6 in the bone marrow are associated with poor outcomes in pediatric acute myeloid leukemia (pAML), but its etiology remains unknown. Using RNA-seq data from pre-treatment bone marrows of 1489 children with pAML, we show that > 20% of patients have concurrent IL-6, IL-1, IFNα/ß, and TNFα signaling activity and poorer outcomes. Targeted sequencing of pre-treatment bone marrow samples from affected patients (n = 181) revealed 5 highly recurrent patterns of somatic mutation. Using differential expression analyses of the most common genomic subtypes (~60% of total), we identify high expression of multiple potential drivers of inflammation-related treatment resistance. Regardless of genomic subtype, we show that JAK1/2 inhibition reduces receptor-mediated inflammatory signaling by leukemic cells in-vitro. The large number of high-risk pAML genomic subtypes presents an obstacle to the development of mutation-specific therapies. Our findings suggest that therapies targeting inflammatory signaling may be effective across multiple genomic subtypes of pAML.

A qualitative study of provider feedback on the feasibility and acceptability of virtual patient simulations for suicide prevention training.

Background: Healthcare organizations are often committed to preventing suicide among their patients, but they can struggle to adequately train providers and implement strategies grounded in evidence-based suicide prevention practices. Virtual patient simulations (VPS) offer the opportunity for providers at healthcare organizations and educational institutions to learn suicide prevention strategies using a realistic and risk-free environment. The purpose of this study was to gather feedback from leaders in the healthcare field regarding the feasibility and acceptability of VPS for their organizations. Methods: Participants (N=9) included administrators, managers, and educators from a variety of health care settings. They were invited to independently test the VPS and participate in a subsequent focus group to provide feedback. Participants were asked about VPS acceptability, satisfaction, potential fit within the intended context, feasibility of delivery, motivation to use, and likelihood of adoption. Responses were audio recorded and transcribed for coding and thematic analysis. Results: Themes emerged regarding perceived benefits of the VPS, considerations related to cost, barriers to implementation, and suggestions for improvement. Participants reported VPS trainings were acceptable and feasible, filling an important gap in the field especially around suicide safety planning, particularly for newer clinicians and students in training. Participants felt that this type of virtual training was particularly feasible given the recent increase in need for online trainings. Suggested improvements included the need to normalize the trial-and-error nature of the VPS for trainees prior to the start of the training, and to consider shortening the duration of the simulation due to learners not being able to bill for time while training. Conclusions: VPS may help to fill an important training need in the field of suicide prevention. The training suite may be best suited for certain settings, such as educational institutions, and most useful for populations including students and new clinicians. VPS may be particularly feasible for organizations that already utilize remote options for work and training.

Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron-deficient mouse pregnancies.

Erythroferrone (ERFE) is an erythroblast-secreted regulator of iron metabolism. The production of ERFE increases during stress erythropoiesis, leading to decreased hepcidin expression and mobilization of iron. Pregnancy requires a substantial increase in iron availability to sustain maternal erythropoietic expansion and fetal development and is commonly affected by iron deficiency. To define the role of ERFE during iron-replete or iron-deficient pregnancy, we utilized mouse models expressing a range of ERFE levels: transgenic (TG) mice overexpressing ERFE, wild-type (WT), and ERFE knockout (KO) mice. We altered maternal iron status using diets with low or standard iron content and performed the analysis at E18.5. Iron deficiency increased maternal ERFE in WT pregnancy. Comparing different maternal genotypes, ERFE TG dams had lower hepcidin relative to their liver iron load but similar hematological parameters to WT dams on either diet. In ERFE KO dams, most hematologic and iron parameters were comparable to WT, but mean corpuscular volume (MCV) was decreased under both iron conditions. Similar to dams, TG embryos had lower hepcidin on both diets, but their hematologic parameters did not differ from those of WT embryos. ERFE KO embryos had lower MCV than WT embryos on both diets. The effect was exacerbated under iron-deficient conditions where ERFE KO embryos had higher hepcidin, lower Hb and Hct, and lower brain iron concentration compared to WT embryos, indicative of iron restriction. Thus, under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis.

COVID-Delayed Elective Surgery Has a Negative Effect on Young Sports Medicine Patients.

Purpose: The purpose of this study was to evaluate the physical and psychological effects of COVID-related elective surgery delays on young sports medicine patients. Methods: We conducted a cross-sectional study of patients (10-25 years old) who had elective sports medicine surgery delayed due to the COVID crisis. Electronic surveys were sent to patients and included the 12-item Short Form Health Survey (SF-12), which yields a physical component score (SF12-PCS) and a mental component score (SF12-MCS), the PROMIS Psychological Stress Experience survey (PROMIS-PSE), and self-designed questions about patient concerns regarding the COVID crisis and delayed surgery. Results: Of the 194 eligible patients with delayed elective sports surgeries, 107 patients (55%) elected to participate (mean age 17.6 ± 3.09 years, 30% male). The mean surgical delay was 76 days (CI 57-98). Delayed surgery patients scored significantly lower than population norms on the SF12-PCS (mean 39.3, CI 37.0-41.7; P < .001). Males scored significantly higher than females on the SF12-MCS (52.8 vs 45.7; P = .002), but the overall SF12-MCS mean was not significantly different from the general population (47.4; P =.07). The mean PSE score was significantly higher than population norms (57.7, CI 56.1-59.3; P < .001), but they did not differ by age or gender. Patients who reported higher levels of concern about their surgical delay endorsed significantly lower scores on the SF-MCS (P = .006) and higher scores on the PROMIS-PSE (P < .001), indicating greater emotional symptoms. The biggest concern with COVID-related surgical delays was a concern about not being back in time for a sports season. Conclusions: Young sports medicine patients reported significant physical and emotional symptoms associated with COVID-related surgical delays. Patients were most concerned about delays resulting in missed sport seasons. Those who reported greater levels of concern with surgical delays reported more emotional symptoms and higher levels of psychological stress. Clinical Relevance: It is important to understand the impact of delayed elective surgical treatment on young patients due to COVID. This study will allow us to make more informed choices for patients during the pandemic.

Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism.

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs). In both samples, predicted pathogenic (PP) heteroplasmies in children are associated with ASD risk (Meta-OR = 1.56, P = 0.00068). Inter-generational transmission of mtDNA reveals attenuated effects of purifying selection on maternal heteroplasmies in children with ASD relative to controls, particularly among males. Among children with ASD and PP heteroplasmies, increased mtDNA content shows benefits for cognition, communication, and behaviors (P ≤ 0.02). These results underscore the value of exploring maternal and newborn mtDNA in ASD.

Older adult driving performance assessed under simulated and on-road conditions.

Simulated driving offers a convenient test of driving ability for older drivers, although the viability of using simulated driving with this population is mixed. The relative weighting of the relevant perceptual, cognitive, and physical factors may vary between simulated and on-road driving. The current study was designed to assess this possibility. We conducted simulated and on-road driving tests of 61 older adults aged 66-92 years. To ensure that the driving performance was measured similarly between the two driving modalities, we employed the Record of Driving Errors (RODE) driving assessment system during both driving tests. Correlation and random weights analysis (RWA) results indicated only modest evidence of correspondence between the simulated and on-road driving performances. The primary factors operative in both simulated and on-road driving was Useful Field of View and a measure of basic cognition. Unique factors for simulated driving included a measure of physical mobility (Time-Up-and-Go) and spatial reasoning (Line), and for on-road driving included chronological age and sensorimotor processing (Trail-Making Task A). Chronological age was correlated primarily the on-road rather than simulated test, was greatly reduced with the inclusion of additional explanatory factors, and likely reflects driving efficiency rather than driving safety. We conclude that simulated driving in healthy older drivers can be beneficial for research purposes to assess cognitive and perceptual factors that underly driving effectiveness, although it cannot serve as a clear proxy for on-road driving.