Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture.

BACKGROUND: The Keap1-Nrf2 pathway serves as a central regulator that mediates transcriptional responses to xenobiotic and oxidative stimuli. Recent studies have shown that Keap1 and Nrf2 can regulate transcripts beyond antioxidant and detoxifying genes, yet the underlying mechanisms remain unclear. Our research has uncovered that Drosophila Keap1 (dKeap1) and Nrf2 (CncC) proteins can control high-order chromatin structure, including heterochromatin. METHODS AND RESULTS: In this study, we identified the molecular interaction between dKeap1 and lamin Dm0, the Drosophila B-type lamin responsible for the architecture of nuclear lamina and chromatin. Ectopic expression of dKeap1 led to an ectopic localization of lamin to the intra-nuclear area, corelated with the spreading of the heterochromatin marker H3K9me2 into euchromatin regions. Additionally, mis-regulated dKeap1 disrupted the morphology of the nuclear lamina. Knocking down of dKeap1 partially rescued the lethality induced by lamin overexpression, suggesting their genetic interaction during development. CONCLUSIONS: The discovered dKeap1-lamin interaction suggests a novel role for the Keap1 oxidative/xenobiotic response factor in regulating chromatin architecture.

Clinical Characteristics, Treatment, and Outcomes of Veterans with Cerebrospinal Fluid Culture Positive for Gram-Negative Rod Bacteria: A Retrospective Analysis over 18 Years in 125 Veterans Health Administration Hospitals.

Optimal management for patients with bacterial ventriculitis/meningitis due to Gram-negative rods (GNRs) has yet to be well investigated. We assessed the clinical characteristics, treatment, and outcomes of patients with a positive cerebrospinal fluid (CSF) culture for GNRs. We conducted a retrospective cohort study of all patients with a positive CSF culture within the Veterans Health Administration (VHA) system during 2003-2020. Clinical and microbiological characteristics between the true meningitis and contamination groups were compared. Of the 5919 patients with positive CSF cultures among 125 nationwide VHA acute-care hospitals, 297 (5.0%) were positive for GNRs. Among 262 patients analyzed, 156 (59.5%) were assessed as patients with true meningitis, and 106 (40.5%) were assessed as patients with contaminated CSF cultures. Patients with true meningitis had a significantly higher CSF protein (median 168 vs 57 mg/dL, p < 0.001), CSF white blood cell count (median 525 vs 3/µL, p = 0.008) and percentage of neutrophils in CSF (median 88 vs 4%, p < 0.001). Enterobacterales were more common in the true meningitis group, while unidentified GNR or polymicrobial CSF cultures were more common in the contamination group. The all-cause 90-day mortality was 25.0% (39/156) in patients with true meningitis and 10.4% (11/106) in those with contaminated CSF cultures. None of the 11 patients with contaminated CSF cultures who died were considered due to missed meningitis. More than 40% of patients with a positive CSF culture with GNR did not receive treatment without negative consequences. Careful clinical judgment is required to decide whether to treat such patients.

Drosophila Keap1 xenobiotic response factor regulates developmental transcription through binding to chromatin.

The Keap1-Nrf2 complex is a central regulator that mediates transcriptional responses to xenobiotic stimuli and is highly related with multiple human diseases. The molecular mechanisms and biological functions of Keap1 and Nrf2 are not fully understood. The Drosophila Keap1 homolog (dKeap1) is conserved with mammalian Keap1 except that dKeap1 contains a 156 aa C-terminal tail (CTD). A dKeap1 truncation with the CTD removed (dKeap1-ΔCTD) shows abolished nuclear localization and chromatin-binding. Expression of dKeap1-ΔCTD in the dKeap1 null background significantly rescues this mutant to the adult stage, but the files showed partial lethality, sterility and defects in adipose tissue. In the rescued flies, expression levels of ecdysone-response genes, ecdysone-synthetic genes and adipogenesis genes were down-regulated in specific tissues, indicating that the chromatin-binding of dKeap1 mediates the activation of these developmental genes. At the same time, dKeap1-ΔCTD can still suppress the basal expression of detoxifying genes and mediate the activation of these genes in response to xenobiotic stimuli, suggesting that the chromatin-binding of dKeap1 is not required for the regulation of detoxifying genes. These results support a model in which dKeap1 on one hand functions as an inhibitor for the Nrf2-mediated transcription in the xenobiotic response pathway and on the other hand functions as a chromatin-binding transcription activator in the developmental pathway. Our study reveals a novel mechanism whereby Keap1-Nrf2 xenobiotic response signaling regulates development using a mechanism independent of redox signaling.

Clinician confidence and practices for evaluating bone health in male and female adolescents and young adults with an eating disorder.

Extensive literature exists on bone health in females with an eating disorder, yet few have studied males. Our study assessed clinician confidence and current practices for assessing bone health in patients with an eating disorder. We also aimed to identify any differences in practice based on patient sex. Our 31-item survey, distributed to adolescent clinicians in the United States via the Society for Adolescent Health and Medicine (SAHM) listserv, assessed clinician confidence and practices for assessing bone mineral density in both male and female adolescents with an eating disorder. Findings showed that clinicians (n = 104) were less confident in assessing bone mineral density in males compared to females (p < .001), yet there was no significant difference in rates of obtaining a DXA (p = .390). Although clinicians are less confident assessing bone health in males with an eating disorder than females, this does not appear to result in screening differences.

To meat or not to meat: disordered eating and vegetarian status in university students.

PURPOSE: This study sought to examine associations between meat-restricted diets and disordered eating cognitions and behaviors in a large sample of university students and assess the relationships between motivations for choosing a vegetarian or semi-vegetarian diet and eating patterns. METHODS: University students (n = 1585; 60%F, 40%M, mean age 20.9) completed an online survey; students were categorized into vegetarians, semi-vegetarians, and non-vegetarians. Vegetarians and semi-vegetarians were sub-categorized into groups: those who cited weight or health among their reasons for adopting the diet and those who reported other reasons (e.g., religion). Outcomes were Eating Disorder Examination Questionnaire (EDE-Q) scores and rates of disordered eating behaviors. RESULTS: Vegetarians comprised 8.6% (32M, 104F) and semi-vegetarians comprised 3.2% (6M, 45F) of the sample; 25% of vegetarians (n = 34) and 65% of semi-vegetarians (n = 33) chose the diet for weight or health-related reasons. Semi-vegetarians scored the highest on measures of eating disorder cognitions and were the most likely to report engaging in disordered eating behaviors, with vegetarians at intermediate risk and non-vegetarians the least likely to report disordered cognitions or behaviors. Semi-vegetarians adopting the diet for reasons of weight or health were at especially high risk compared to other semi-vegetarians, while no associations were found between motivations for adopting a vegetarian diet and disordered eating patterns. CONCLUSION: Semi-vegetarians, especially those adopting the diet for reasons of weight or health, are more likely to exhibit disordered eating cognitions and behaviors compared to vegetarians and non-vegetarians. LEVEL OF EVIDENCE: Level III, cohort study.

Clinician practices assessing hypothalamic-pituitary-gonadal axis suppression in adolescents with an eating disorder.

OBJECTIVE: Although extensive literature exists on hypothalamic-pituitary-gonadal (HPG) axis suppression in females with an eating disorder, there are few studies in males. Our study aimed to determine clinician practices for the assessment of HPG axis suppression and to identify differences in practice based on the sex of the patient. METHOD: Our 31-item survey queried clinicians about confidence level and practices for assessing HPG suppression in male compared to female patients. RESULTS: Findings showed that clinicians (n = 104) were less likely to evaluate HPG suppression in males compared to females, including assessment of sexual maturity rating (p < .050), screening of decreased libido compared to amenorrhea (p < .001) and lab assessment (luteinizing hormone and follicular-stimulating hormone: p < .001; estradiol/testosterone: p < .010; TSH: p < .050). Participants also felt less confident evaluating male patients (p < .001) and requested better screening tools for males (p < .001). DISCUSSION: Our data suggest that clinician practices differ based on patient sex and that clinicians request tools for HPG suppression assessment in males. This is the first study examining specific practices and comfort levels of clinicians when assessing HPG axis suppression. Findings suggest that more guidance on the management of male patients may be needed to standardize care and to prevent short and long-term sequela of malnutrition.

Associations between ergogenic supplement use and eating behaviors among university students.

Ergogenic supplements to improve athletic performance are commonly used among college athletes, but little is known about their association with eating disorder symptoms. The objective of this study was to examine associations between ergogenic supplement use and disordered eating attitudes and behaviors among university students, and to compare differences by sex. Undergraduate students from 10 top-ranked National College Athletics Association (NCAA) Division I colleges completed an online survey on supplement use, athletic activities, and eating attitudes and behaviors. Among 1633 university students, males (38.9%) reported higher rates of current supplement use than females (15.2%) (p < .001). In linear regression models adjusting for athletic status and body mass index, current supplement use was associated with higher Eating Disorders Examination-Questionnaire (EDE-Q) Global, Shape Concern, and Restraint scores in both males and females. Supplement use was associated with driven/compelled exercise (OR 2.00, 95% CI 1.33-2.99) in males and diuretic (OR 6.39, 95% CI 2.02-20.22) and diet pill use (OR 3.07, 95% CI 1.79-5.27) in females. Results suggest ergogenic supplement use is common in undergraduates and associated with disordered eating attitudes and behaviors. Clinicians should screen for disordered eating behaviors particularly in young adults who use ergogenic supplements.

Eating behavior and reasons for exercise among competitive collegiate male athletes.

PURPOSE: Research concerning eating disorders among adolescent and young adult male athletes is limited compared with female counterparts, but increasing evidence indicates that they may be at unique risk for unhealthy exercise and eating behavior. The current study aimed to characterize unhealthy exercise and eating behavior according to competitive athlete status, as well as per sport type. METHOD: Collegiate male athletes (N = 611), each affiliated with one of the 10 National College Athletics Association (NCAA) Division I schools in the United States, completed an online survey, reporting on eating and extreme weight control behaviors, and reasons for exercise. RESULTS: Competitive athletes endorsed increased driven exercise and exercising when sick. Baseball players, cyclists, and wrestlers emerged as the sports with the most players reporting elevated Eating Disorder Examination-Questionnaire scores in a clinical range, and basketball players reported the highest rates of binge eating. overall, baseball players, cyclists, rowers, and wrestlers appeared to demonstrate the greatest vulnerability for unhealthy eating and exercise behavior. CONCLUSION: Findings revealed differences between competitive and non-competitive male athletes. Among competitive athletes, results identified unique risk for unhealthy eating and exercise behavior across a variety of sport categories and support continued examination of these attitudes and behaviors in a nuanced manner. LEVEL II: Evidence obtained from well-designed controlled trials without randomization.

Low-Energy Availability and the Electronic Preparticipation Examination in College Athletes: Is There a Better Way to Screen?

ABSTRACT: The electronic preparticipation physical examination (ePPE) is commonly used to identify health conditions that would affect participation in sports for athletes, including disordered eating and/or low energy availability (EA). A secondary analysis was performed using a cohort study of female college athletes attending a Division 1 university between 2008 and 2014. Descriptive statistics and logistic regression analyses were used to explore the association between responses to questions on the ePPE related to eating behaviors and Female Athlete Triad (Triad). Risk categories (low, moderate, or high) were assigned to 239 athletes participating in 16 sports. The majority of responses on the ePPE did not identify athletes associated with moderate-/high-risk categories. Our findings suggest that ePPE may not sufficiently identify athletes at elevated risk for health concerns of the Triad. Our findings suggest that future ePPE may consider validated screening tools for disordered eating to help identify athletes at risk of low EA.

The State of Cancer Care in America: Impact of State Policy on Access to High-Quality Cancer Care.

Health policy in America has shifted rapidly over the last decade, and states are increasingly exercising greater authority over health policy decision-making. This localization and regionalization of healthcare policy poses significant challenges for patients with cancer, providers, advocates, and policymakers. To identify the challenges and opportunities that lay ahead of stakeholders, NCCN hosted the 2019 Policy Summit: The State of Cancer Care in America on June 27, 2019, in Washington, DC. The summit featured multidisciplinary panel discussions to explore the implications for access to quality cancer care within a shifting health policy landscape from a patient, provider, and lawmaker perspective. This article encapsulates the discussion from this NCCN Policy Summit.

Regulation of position effect variegation at pericentric heterochromatin by Drosophila Keap1-Nrf2 xenobiotic response factors.

The Keap1-Nrf2 signaling pathway plays a central role in the regulation of transcriptional responses to oxidative species and xenobiotic stimuli. The complete range of molecular mechanisms and biological functions of Keap1 and Nrf2 remain to be fully elucidated. To determine the potential roles of Keap1 and Nrf2 in chromatin architecture, we examined the effects of their Drosophila homologs (dKeap1 and CncC) on position effect variegation (PEV), which is a transcriptional reporter for heterochromatin formation and spreading. Loss of function mutations in cncC, dKeap1, and cncC/dKeap1 double mutants all suppressed the variegation of wm4 and SbV PEV alleles, indicating that reduction of CncC or dKeap1 causes a decrease of heterochromatic silencing at pericentric region. Depletion of CncC or dKeap1 in embryos reduced the level of the H3K9me2 heterochromatin marker, but had no effect on the transcription of the genes encoding Su(var)3-9 and HP1. These results support a potential role of dKeap1 and CncC in the establishment and/or maintenance of pericentric heterochromatin. Our study provides preliminary evidence for a novel epigenetic function of Keap1-Nrf2 oxidative/xenobiotic response factors in chromatin remodeling.

Comparisons of bone density and body composition among adolescents with anorexia nervosa and atypical anorexia nervosa.

OBJECTIVE: To compare bone mineral density (BMD) and body composition among adolescents: (a) with atypical anorexia nervosa (AAN) versus anorexia nervosa (AN) and (b) those with and without a prior history of overweight. METHOD: Electronic medical records of patients 9-20 years with AN or AAN who underwent dual-energy x-ray absorptiometry scans were retrospectively reviewed and analyzed. RESULTS: A total of 286 adolescents with AN or AAN were included. In linear regression models, AAN was associated with greater Z-scores in whole body bone mineral content (BMC, B = 0.88, p < 0.001), lumbar spine BMD (B = 0.79, p = 0.002), femoral neck BMD (B = 0.670, p = 0.009); fat mass index (B = 1.33, p = 0.003), and lean body mass index (LBMI, B = 1.10, p < 0.001) compared to AN, adjusting for age, sex, and duration of illness. A prior overweight history was associated with greater Z-scores in whole body BMC; lumbar spine BMD, total hip BMD, femoral neck BMD, and LBMI. DISCUSSION: Adolescents with AAN had higher BMD Z-scores than adolescents with AN; adolescents with a prior overweight history had greater BMD Z-scores than adolescents without a prior overweight history. These findings may inform clinical guidelines for the medical management of AAN.

Associations between exercise, bone mineral density, and body composition in adolescents with anorexia nervosa.

OBJECTIVE: To identify the effect of duration of weight-bearing exercise and team sports participation on bone mineral density (BMD) and body composition among adolescents with anorexia nervosa (AN). METHOD: We retrospectively reviewed electronic medical records of all patients 9-20 years old with a DSM-5 diagnosis of AN evaluated by the Stanford Eating Disorders Program (1997-2011) who underwent dual-energy X-ray absorptiometry. RESULTS: A total of 188 adolescents with AN were included (178 females and 10 males). Using multivariate linear regression, duration of weight-bearing exercise (B = 0.15, p = 0.005) and participation in team sports (B = 0.53, p = 0.001) were associated with higher BMD at the hip and team sports (B = 0.39, p = 0.006) were associated with higher whole body BMC, controlling for covariates. Participation in team sports (B = - 1.06, p = 0.007) was associated with greater deficits in FMI Z-score. LBMI Z-score was positively associated with duration of weight-bearing exercise (B = 0.10, p = 0.018) and may explain the relationship between exercise and bone outcomes. CONCLUSION: Duration of weight-bearing exercise and team sports participation may be protective of BMD at the hip and whole body BMC, while participation in team sports was associated with greater FMI deficits among adolescents with AN. LEVEL OF EVIDENCE: Level V, descriptive retrospective study.

Assessment of sex differences in bone deficits among adolescents with anorexia nervosa.

OBJECTIVE: The objective of this study was to compare sex differences in bone deficits among adolescents with anorexia nervosa (AN) and to identify other correlates of bone health. METHOD: Electronic medical records of all patients 9-20 years of age with a DSM-5 diagnosis of AN who were evaluated by the eating disorders program at Stanford with dual-energy X-ray absorptiometry (DXA) between March 1997 and February 2011 were retrospectively reviewed. Whole body bone mineral content Z-scores and bone mineral density (BMD) Z-scores at multiple sites were recorded using the Bone Mineral Density in Childhood Study (BMDCS) reference data. RESULTS: A total of 25 males and 253 females with AN were included, with median age 15 years (interquartile range [IQR] 14-17) and median duration of illness 9 months (IQR 5-13). Using linear regression analyses, no significant sex differences in bone deficits were found at the lumbar spine, total hip, femoral neck, or whole body when controlling for age, %mBMI, and duration of illness. Lower %mBMI was significantly associated with bone deficits at all sites in adjusted models. DISCUSSION: This is the first study to evaluate sex differences in bone health among adolescents with AN, using novel DSM-5 criteria for AN and robust BMDCS reference data. We find no significant sex differences in bone deficits among adolescents with AN except for a higher proportion of females with femoral neck BMD Z-scores <-1. Degree of malnutrition was correlated with bone deficits at all sites. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:352-358).

Characterization and correlates of exercise among adolescents with anorexia nervosa and bulimia nervosa.

OBJECTIVE: To characterize exercise behaviors among adolescents with anorexia nervosa (AN), atypical AN, or bulimia nervosa (BN), and determine associations between exercise and medical risk. STUDY DESIGN: Cross-sectional electronic medical records of all patients evaluated by the Eating Disorder Program at Stanford between January 1997 and February 2011 were retrospectively reviewed. RESULTS: 1,083 subjects (961 females, 122 males; mean age 15.6) met eligibility criteria. Most patients (89.7%) reported exercise (mean 7.0 h per week over mean 5.4 days per week) prior to presentation. Running (49.9%), calisthenics (40.7%), walking (23.4%), soccer (20.9%), and swimming (18.2%) were the most common exercises; a majority (60.6%) reported team sport participation. Males were less likely to report team exercise (p = .005). Bradycardia (heart rate <50) at presentation was associated with team sport participation (adjusted odds ratio [AOR] 1.66, 95% confidence interval [CI] 1.02-2.72) and hours of exercise per week (AOR 1.05, 95% CI 1.02-1.09), controlling for diagnosis, sex, age, duration of illness, rate of weight loss, and percent median body mass index (%mBMI). DISCUSSION: Adolescents with AN, atypical AN, and BN reported high levels of exercise. Females reported more team sport participation. Greater exercise frequency and team sport participation were associated with bradycardia. Further studies assessing the relationship between exercise and bradycardia may help inform the medical management of adolescents with these eating disorders who are more physically active.

Application of organic amendments to restore degraded soil: effects on soil microbial properties.

Topsoil removal, compaction, and other practices in urban and industrial landscapes can degrade soil and soil ecosystem services. There is growing interest to remediate these for recreational and residential purposes, and urban waste materials offers potential to improve degraded soils. Therefore, the objective of this study was to compare the effects of urban waste products on microbial properties of a degraded industrial soil. The soil amendments were vegetative yard waste compost (VC), biosolids (BioS), and a designer mix (DM) containing BioS, biochar (BC), and drinking water treatment residual (WTR). The experiment had a completely randomized design with following treatments initiated in 2009: control soil, VC, BioS-1 (202 Mg ha(-1)), BioS-2 (403 Mg ha(-1)), and DM (202 Mg BioS ha(-1) plus BC and WTR). Soils (0-15-cm depth) were sampled in 2009, 2010, and 2011 and analyzed for enzyme activities (arylsulfatase, ß-glucosaminidase, ß-glucosidase, acid phosphatase, fluorescein diacetate, and urease) and soil microbial community structure using phospholipid fatty acid analysis (PLFA). In general, all organic amendments increased enzyme activities in 2009 with BioS treatments having the highest activity. However, this was followed by a decline in enzyme activities by 2011 that were still significantly higher than control. The fungal PLFA biomarkers were highest in the BioS treatments, whereas the control soil had the highest levels of the PLFA stress markers (P < 0.10). In conclusion, one-time addition of VC or BioS was most effective on enzyme activities; the BioS treatment significantly increased fungal biomass over the other treatments; addition of BioS to soils decreased microbial stress levels; and microbial measures showed no statistical differences between BioS and VC treatments after 3 years of treatment.

Finalizing emergency management professionalization in 2024.

This editorial discusses the urgent need to finalize the emerging emergency management profession. Points of reference in the years immediately preceding and throughout the COVID-19 pandemic are recounted and frame some of the essential forward work slated to be started or completed this year in 2024. Activity taking place by connected associations and members of the emerging profession is shared. Legislation filed in Massachusetts to finalize the emerging profession is also shared. Activities needed for the emerging profession are described, and how professionals can help in their role to continue to move these fundamental initiatives forward is outlined. Present considerations should be accounted for, as they threaten the fabric of the emerging profession while at the same time giving us undeniable reasons for why we need to finalize this critical work in 2024 before the next major global disaster.

Medical Considerations and Consequences of Eating Disorders.

Eating disorders may result in medical complications that affect every body system with both acute and chronic consequences. Although some medical complications may require acute medical hospitalization to manage, other complications, such as low bone mineral density, may not present until malnutrition has become chronic. It is critical for team members to be aware of the early clinical signs of malnutrition and disordered eating behaviors, as well as longer-term complications that may affect their patients. When identifying eating disorder concerns, appropriate colleagues from the medical, nutrition, and psychiatric fields can be engaged in order to collaborate on stabilizing and improving the health of patients.

The association between overuse and musculoskeletal injuries and the female athlete triad in Division I collegiate athletes.

INTRODUCTION: Although the female athlete triad (Triad) has been associated with increased risk of bone-stress injuries (BSIs), limited research among collegiate athletes has addressed the associations between the Triad and non-BSI injuries. OBJECTIVE: To elucidate the relationship between Triad and both BSI and non-BSI in female athletes. DESIGN: Retrospective cohort study. SETTING: Primary and tertiary care student athlete clinic. PARTICIPANTS: National Collegiate Athletic Association Division I female athletes at a single institution. INTERVENTION: Participants completed a pre-participation questionnaire and dual-energy x-ray absorptiometry, which was used to generate a Triad cumulative risk assessment score (Triad score). The number of overuse musculoskeletal injuries that occurred while the athletes were still competing collegiately were identified through chart review. MAIN OUTCOME MEASURE: BSI and non-BSI were treated as count variables. The association between BSI, non-BSI, and Triad score was measured using Poisson regression to calculate rate ratios. RESULTS: Of 239 athletes, 43% of athletes (n = 103) sustained at least one injury. Of those, 40% (n = 95) sustained at least one non-BSI and 10% (n = 24) sustained at least one BSI over an average follow-up 2.5 years. After accounting for sport type (non-lean, runner, other endurance sport, or other lean advantage sport) and baseline age, we found that every additional Triad score risk point was associated with a significant 17% increase in the rate of BSI (rate ratio [RR] 1.17, 95% confidence interval [CI] 1.03-1.33; p = .016). However, Triad score was unrelated to non-BSI (1.00, 95% CI 0.91-1.11; p = .99). Compared with athletes in non-lean sports (n = 108), athletes in other lean advantage sports (n = 30) had an increased rate of non-BSI (RR: 2.09, p = .004) whereas distance runners (n = 46) had increased rates of BSI (RR: 7.65, p < .001) and non-BSI (RR: 2.25, p < .001). CONCLUSIONS: Higher Triad score is associated with an increased risk of BSI but not non-BSI in collegiate athletes.