Disparities in Child Welfare Referrals for Patients Seen in a Pediatric Emergency Department for Unintentional Ingestions.

OBJECTIVE: To examine the characteristics of patients visiting the pediatric emergency department (PED) for unintentional ingestions and associations between patient race and ethnicity in referrals to Child Protective Services (CPS) for supervisory neglect. METHODS: We conducted a cross-sectional analysis of children <12 years old who presented to the PED between October 2015 and December 2020 for an unintentional ingestion. Patients were identified by searching the electronic health record for diagnosis codes corresponding to unintentional ingestions. Patient demographics, ingestion type, disposition, and referrals to CPS were abstracted by manual chart review. Logistic regression models were used to evaluate associations between patient demographics and visit characteristics with referral to CPS. RESULTS: We identified 129 PED encounters for unintentional ingestions that were included for analysis. Overall, 22 patients (17.1%) were referred to CPS for neglect. In the univariate analysis, both ingestion of an illicit drug and arrival to the PED by ambulance were associated with a higher odds of referral to CPS. In the multivariable model adjusted for parent language, ingestion type, and mode of arrival to the PED, Hispanic patients had higher odds of referral to CPS than White patients (adjusted odds ratio (aOR) = 17.2, 95% confidence intervals [1.8-162.3], P = .03). There was not a statistically significant association between Black race and referral to CPS. CONCLUSIONS: Referrals to CPS from the PED after unintentional ingestions are common and disproportionally involve Hispanic patients. More research is needed to promote equitable child maltreatment reporting for children presenting to the PED following unintentional ingestions.

Disparities in use of physical restraints at an urban, minority-serving hospital emergency department.

BACKGROUND: Recent reports have identified associations between patient race and ethnicity and use of physical restraint while receiving care in the emergency department (ED). However, no study has assessed this relationship in hospitals primarily treating patients of color and underserved populations. The primary objective of this study was to evaluate the association between race/ethnicity and the use of restraints in an ED population at a minority-serving, safety-net institution. METHODS: For this cross-sectional study, chart review identified all adult patients presenting to the Boston Medical Center ED between January 2018 and April 2021. Generalized estimating equation logistic regression modeling was conducted to evaluate associations between race and use of restraints. RESULTS: Of 348,384 ED visits (22.9% White, 46.7% Black, 23.1% Hispanic), 1852 (0.5%) had an associated physical restraint order. Multivariable models showed significant interactions (p = 0.02) between race/ethnicity, behavioral health diagnosis, and sex on the primary outcome of physical restraint. Stratified analysis revealed that among patients with no behavioral health diagnoses, Black (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.34-0.72, p = 0.0003) and Hispanic (OR 0.35, 95% CI 0.20-0.63, p = 0.0004) patients had lower odds of restraint than White patients. Among female patients with a mental health and/or substance use disorder diagnosis, Black (OR 1.95, 95% CI 1.49-2.54, p < 0.0001) and Hispanic (OR 2.13, 95% CI 1.49-3.03, p < 0.0001) patients had higher odds of restraint than White patients. Similar trends were observed for Black male patients (OR 1.60, 95% CI 1.34-1.91, p < 0.0001) but not for Hispanic male patients (OR 0.96, 95% CI 0.73-1.26, p = 0.77) with behavioral health diagnoses who had similar odds of restraint to White patients. Additional factors associated with physical restraint include younger age, public or lack of insurance, and ED visits during the pandemic. CONCLUSIONS: Racial disparities exist in restraint utilization at this minority-serving safety-net hospital; however, these disparities are modified by sex and by behavioral health diagnoses. The reasons for these disparities may be multifactorial and warrant further investigation.

Differences in Risks for Recurrent Injury and Death Among Survivors of Violence by Homeless Status.

A better understanding of the unique risks for survivors of violence experiencing homelessness could enable more effective intervention methods. The aim of this study was to quantify the risks of death and reinjury for unhoused compared to housed survivors of violent injuries. This retrospective study included a cohort of patients with known housing status presenting to the Boston Medical Center Emergency Department between 2009 and 2018 with a violent penetrating injury. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risks of all-cause mortality and violent reinjury. Of the 2330 patients included for analysis, 415 (17.8%) were unhoused at the time of index injury. Within 3 years of the index injury, there were 319 (13.9%) violent reinjuries and 55 (2.4%) deaths. Unhoused patients were more likely than housed patients to be violently reinjured by all causes (HR = 1.39, 95% CI = 1.06-1.83, p = 0.02), by stab wound (HR = 2.34, 95% CI = 1.33-4.11, p = 0.0003), and by blunt assault (HR = 1.52, 95% CI = 1.05-2.21, p = 0.03). Housed and unhoused patients were equally likely to die within 3 years of their index injury; however, unhoused patients were at greater risk of dying by homicide (HR = 2.89, 95% CI = 1.34-6.25, p = 0.006) or by a drug/alcohol overdose (HR = 2.86, 95% CI = 1.17-6.94, p = 0.02). In addition to the already high risks that all survivors of violence have for recurrent injuries, unhoused survivors of violence are at even greater risk for violent reinjury and death and fatal drug/alcohol overdose. Securing stable housing for survivors of violence experiencing homelessness, and connecting them with addiction treatment, is essential for mitigating these risks.

Exposure to Neighborhood Racialized Economic Segregation and Reinjury and Violence Perpetration Among Survivors of Violent Injuries.

Importance: Much is unknown about how individual and neighborhood factors converge in the association with risk for violent reinjury and violence perpetration. Objectives: To investigate the association of exposure to neighborhood racialized economic segregation with reinjury and use of violence against others among survivors of violent penetrating injury. Design, Setting, and Participants: This retrospective cohort study was performed using data obtained from hospital, police, and state vital records. The study was performed at Boston Medical Center, an urban, level I trauma center that is the largest safety-net hospital and busiest trauma center in New England. The cohort included all patients treated for a nonfatal violent penetrating injury from 2013 to 2018. Patients with no Boston metropolitan area home address were excluded. Individuals were followed up through 2021. Data were analyzed from February to August 2022. Exposure: American Community Survey data were used to measure neighborhood deprivation using the racialized economic Index of Concentration at the Extremes (ICE) for patient residential address upon hospital discharge. ICE was measured on a scale from -1 (most deprived) to 1 (most privileged). Main Outcomes and Measures: Primary outcomes were violent reinjury and police-reported perpetration of violence within 3 years of an index injury. Results: Of 1843 survivors of violence (median [IQR] age, 27 [22-37] years; 1557 men [84.5%]; 351 Hispanic [19.5%], 1271 non-Hispanic Black [70.5%], and 149 non-Hispanic White [8.3%] among 1804 patients with race and ethnicity data), the cohort was skewed toward residing in neighborhoods with higher racialized economic segregation (median [IQR] ICE = -0.15 [-0.22 to 0.07]) compared with the state overall (ICE = 0.27). There were police encounters for violence perpetration among 161 individuals (8.7%) and violent reinjuries among 214 individuals (11.6%) within 3 years after surviving a violent penetrating injury. For each 0.1-unit increase in neighborhood deprivation, there was a 13% (hazard ratio [HR], 1.13; 95% CI, 1.03 to 1.25; P = .01) increase in risk of violence perpetration but no difference in risk for violent reinjury (HR, 1.03; 95% CI, 0.96 to 1.11; P = .38). The greatest occurrence for each outcome was within the first year after index injury; for example, incidents of violence perpetration occurred among 48 of 614 patients (7.8%) at year 1 vs 10 of 542 patients (1.8%) at year 3 in tertile 3 of neighborhood deprivation. Conclusions and Relevance: This study found that living in a more economically deprived and socially marginalized area was associated with increased risk of using violence against others. The finding suggests that interventions may need to include investments in neighborhoods with the highest levels of violence to help reduce downstream transmission of violence.

Racial and Ethnic Disparities in Violent Penetrating Injuries and Long-Term Adverse Outcomes.

Violent injury is known to be a chronic, recurrent issue, with high rates of recidivism following initial injury. While the burden of violence is disproportionately felt among young Black men and in communities of color, examination of distinct risk factors and long-term outcomes for other racial and ethnic groups could lead to improved violence intervention strategies. In this study, we examined the risk of violent penetrating injury and long-term adverse outcomes by race and ethnicity. This retrospective study was performed using a cohort of patients presenting to the Boston Medical Center emergency department for a violent penetrating injury between 2006 and 2016. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for the risk of all-cause mortality and violent re-injury at one and 3 years after surviving a penetrating injury.Of the 4191 victims of violent injury, 12% were White, 18% were Hispanic, and the remaining 70% self-identified as Black. Within 3 years after initial injury, Black patients were at the greatest risk of all-cause violent re-injury (vs. Hispanic: HR = 1.46, 95%CI[1.15,1.85], p = 0.002; vs. White: HR = 1.89, 95%CI[1.40,2.57], p < 0.0001), particularly by gunshot wound (vs. Hispanic: HR = 2.04, 95%CI[1.29,3.22] p = 0.002; vs. White: HR = 2.34, 95%CI[1.19,4.60], p = 0.01). At 3-years following initial injury, White patients were at 2.03 times the risk for all-cause mortality, likely due to a 4.96 times greater risk of death by drug or alcohol overdose for White patients compared to Black patients (HR = 4.96, 95%CI[2.25,10.96], p < 0.0001). In conclusion, Black survivors of violent injury have a significantly higher risk of violent re-injury, particularly by gun violence, while White patients are at the highest risk for mortality due to the incidence of drug and alcohol overdose. Violence intervention programs with similar patient populations should explore options to collaborate with drug treatment programs to reach this vulnerable population.

Implementation of a Novel Home Visiting Nurse Pilot Program for Victims of Violent Penetrating Injury.

BACKGROUND: Survivors of violent injuries are at risk for readmission, rehospitalization, and reinjury. In 2017, a novel home visiting nurse pilot program was implemented within a hospital-based violence intervention program (HVIP) to address disparities in care and combat the limited health care literacy and access, and the general mistrust of health care institutions among much of this population. OBJECTIVE: The purpose of this study was to review the design and implementation of the home visiting nurse component of the HVIP and to report the demographics, clinical characteristics, home care needs, and short-term health outcomes of the pilot sample. METHODS: This retrospective study was performed using a cohort of patients presenting to the emergency department at an urban, Level I trauma center for a violent penetrating injury between 2017 and 2018. The χ2 and Wilcoxon rank sum tests were used to compare patient demographics and injury characteristics. Cox proportional hazards regression models were used to estimate health outcomes. RESULTS: Of the 742 victims of violence included in this analysis, the 57 patients enrolled in the home visiting nurse pilot program were more likely to have severe gunshot wounds (68.4% vs. 40.3%, p < .001) requiring hospitalization (80.7% vs. 53.3%, p < .001), with 3.5% requiring rehospitalization within 90 days. The primary interventions provided by the home visiting nurse involved medical navigation and education, wound care, and consultation, underscoring the critical importance of health literacy and outreach for this vulnerable population. CONCLUSION: The nurse-advocate partnership provides the foundation for this novel program to aid a marginalized population in overcoming health inequities.

Trends in Violent Penetrating Injuries During the First Year of the COVID-19 Pandemic.

Importance: Public health measures instituted to reduce the spread of COVID-19 led to severe disruptions to the structure of daily life, and the resultant social and financial impact may have contributed to an increase in violence. Objective: To examine the trends in violent penetrating injuries during the first COVID-19 pandemic year compared with previous years. Design, Setting, and Participants: This retrospective cross-sectional study was performed to compare the prevalence of violent penetrating injuries during the first COVID-19 pandemic year, March 2020 to February 2021, with the previous 5 years, March 2015 to February 2020. This study was performed among all patients with a violent penetrating injury presenting at Boston Medical Center, an urban, level I trauma center that is the largest safety-net hospital and busiest trauma center in New England. Data were analyzed from January 4 to November 29, 2021. Main Outcomes and Measures: The primary outcomes were the incidence and timing of emergency department presentation for violent penetrating injuries during the first year of the COVID-19 pandemic compared with the previous 5 years. Patient demographics and injury characteristics were also assessed. Results: A total of 2383 patients (median [IQR] age, 29.5 [23.4-39.3] years; 2032 [85.4%] men and 351 [14.6%] women) presenting for a violent penetrating injury were evaluated, including 1567 Black patients (65.7%), 448 Hispanic patients (18.8%), and 210 White patients (8.8%). There was an increase in injuries during the first pandemic year compared with the previous 5 years, with an increase in shootings (mean [SD], 0.61 [0.89] injuries per day vs 0.46 [0.76] injuries per day; P = .002) but not stabbings (mean [SD], 0.60 [0.79] injuries per day vs 0.60 [0.82] injuries per day; P = .78). This surge in firearm violence began while Massachusetts was still under a stay-at-home advisory and before large-scale racial justice protests began. Patients presenting with violent penetrating injuries in the pandemic surge months (April-October 2020) compared with the same period in previous years were disproportionately male (153 patients [93.3%] vs 510 patients [87.6%]; P = .04), unemployed (70 patients [57.4%] vs 221 patients [46.6%]; P = .03), and Hispanic (40 patients [26.0%] vs 99 patients [17.9%]; P = .009), with a concurrent decrease in White patients (0 patients vs 26 patients [4.7%]), and were more likely to have no previous history of violent penetrating injury (146 patients [89.0%] vs 471 patients [80.9%]; P = .02). Conclusions and Relevance: These findings suggest that unprecedented measures implemented to mitigate the spread of COVID-19 were associated with an increase in gun violence. As the pandemic abates, efforts at community violence prevention and intervention must be redoubled to defend communities against the epidemic of violence.

Mechanism of penetrating injury mediates the risk of long-term adverse outcomes for survivors of violent trauma.

BACKGROUND: While hospital-based violence intervention programs are primarily designed to aid youth victims of gun violence at high risk for reinjury, the root causes and complex outcomes of community violence are varied. In this study, we examined the risk factors for violent penetrating injury and how the risk of adverse outcomes for survivors differs by injury type (stabbing vs. gunshot wound). METHODS: This retrospective study was performed using a cohort of patients presenting to the Boston Medical Center emergency department for a penetrating injury due to community violence between 2006 and 2016. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of all-cause mortality and violent reinjury within 3 years after surviving a penetrating injury. RESULTS: Of the 4,280 survivors of the initial violent penetrating injury, there were 88 deaths (2.1%) and 568 violent reinjuries (13.3%) within 3 years. Compared with gunshot wound victims, stab wound victims were 31% less likely to be reinjured with a gunshot wound (HR, 0.69; 95% CI, 0.51-0.93), 72% more likely to be reinjured with a stab wound (HR, 1.72; 95% CI, 1.21-2.43), and 49% more likely to be reinjured by assault (HR, 1.49; 95% CI, 1.14-1.94). While survivors of stabbing and firearm injuries were equally at risk for 3-year all-cause mortality, stab wound victims were 3.75 times more likely to die by a drug/alcohol overdose (HR, 3.75; 95% CI, 1.11-20.65). CONCLUSION: Patients surviving a stab wound have a significantly higher risk of violent reinjury by stabbing or assault, and risk of death by drug/alcohol overdose. Hospital-based violence intervention programs with similar patient populations should explore options to expand partnerships with drug treatment programs. These results illustrate two distinct populations of victims of violence-gunshot victims and stabbing/assault victims-with separate risk factors and outcomes, mediated by substance use disorder. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; level III.

Boston Violence Intervention Advocacy Program: Challenges and Opportunities for Client Engagement and Goal Achievement.

OBJECTIVES: A better understanding of the factors affecting client engagement in hospital-based violence intervention programs (HVIPs), and which types of client needs prove most challenging to achieve, may be of key importance in developing novel, targeted strategies to violence intervention. In this study, we examined the demographics and injury characteristics of violently injured patients by their level of engagement with the Boston Violence Intervention Advocacy Program (VIAP) and determined the degree of client goal achievement through VIAP client services. METHODS: This retrospective study was performed using a cohort of patients presenting to the Boston Medical Center emergency department for a violent penetrating injury due to community violence between 2013 and 2018. Data on client demographics, injury characteristics, and client needs were collected from the VIAP data repository. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals to assess the difference in hazards of client goal achievement by need type. RESULTS: Of the 2,243 victims of violent injury, 839 (37.4%) patients engaged with VIAP. Significant predictors of client engagement include younger age, Black race, permanent home, existing mental health diagnosis, gunshot wound, and more severe injuries. Conversely, older age, homelessness, substance use, stab wound, and less severe injuries predicted refusal of VIAP services. For clients who chose to engage with VIAP, needs related to education (HR = 0.47, 95% CI = 0.38 to 0.58), employment (HR = 0.66, 95% CI = 0.57 to 0.77), and housing (HR = 0.76, 95% CI = 0.68 to 0.86) were significantly less likely to be achieved compared to basic needs. CONCLUSIONS: This study demonstrates that VIAP is effectively engaging the client population that HVIPs have been designed to support. HVIPs should consider novel strategies to engage vulnerable populations not typically targeted by intervention programs. These results speak to the difficulties of program attrition and the complexities of altering the life course for victims of violence.

Quantitative Profiling of Lipid Species in Caenorhabditis elegans with Gas Chromatography-Mass Spectrometry.

Gas chromatography-mass spectrometry (GC-MS) enables sensitive detection and relative quantification of fatty acids. In Caenorhabditis elegans, the use of GC-MS can corroborate findings from common staining methodologies, providing great resolution on the lipid species altered in abundance in aging, genetic mutants, or with dietary or pharmacologic manipulation. Here we describe a method to quantitate relative abundance of fatty acids in total worm lipid extracts, as well as a method that quantitates fatty acids following separation into neutral lipid pools (triacylglycerols and cholesteryl esters) versus more polar lipids (phospholipids) by solid-phase extraction (SPE).

Temporal trends of co-diagnosis of depression and/or anxiety among female maternal and non-maternal hospitalizations: Results from Nationwide Inpatient Sample 2004-2013.

Perinatal depression/anxiety is considered the most underdiagnosed pregnancy complication in the US and is associated with poor maternal and fetal outcomes. However, despite its prevalence, most women who present with depressive symptoms are not screened and do not receive adequate treatment. We examined the clinical co-diagnosis of depression and/or anxiety among maternal and non-maternal hospitalizations among females aged 14-49 from the Nationwide Inpatient Sample (NIS) between 2004 and 2013 (n = 83,472,775). Meta-regression was used to determine annual change and presence of temporal trends. Survey logistic regression was used to examine the association with sociodemographic factors. Rates of diagnosis of depression and/or anxiety disorders demonstrated a temporal increase from 2004-2013, and this increase was mainly driven by non-maternal hospitalizations compared to maternal. Furthermore, non-maternal hospitalizations demonstrated a greater prevalence of depression and/or anxiety diagnoses compared to maternal hospitalizations over the same time period (21•7% versus 2•8%). Among all female hospitalizations, whites were roughly twice as likely as minorities to have a diagnosis of depression and/or anxiety. These results add to the evidence suggestive of the underdiagnosed depression/anxiety present among women of reproductive age, particularly pregnant women and minorities, and underscore the critical role of obstetricians in treating both physical and mental health.

Cohort profile: The MULTI sTUdy Diabetes rEsearch (MULTITUDE) consortium.

PURPOSE: Globally, the age-standardised prevalence of type 2 diabetes mellitus (T2DM) has nearly doubled from 1980 to 2014, rising from 4.7% to 8.5% with an estimated 422 million adults living with the chronic disease. The MULTI sTUdy Diabetes rEsearch (MULTITUDE) consortium was recently established to harmonise data from 17 independent cohort studies and clinical trials and to facilitate a better understanding of the determinants, risk factors and outcomes associated with T2DM. PARTICIPANTS: Participants range in age from 3 to 88 years at baseline, including both individuals with and without T2DM. MULTITUDE is an individual-level pooled database of demographics, comorbidities, relevant medications, clinical laboratory values, cardiac health measures, and T2DM-associated events and outcomes across 45 US states and the District of Columbia. FINDINGS TO DATE: Among the 135 156 ongoing participants included in the consortium, almost 25% (33 421) were diagnosed with T2DM at baseline. The average age of the participants was 54.3, while the average age of participants with diabetes was 64.2. Men (55.3%) and women (44.6%) were almost equally represented across the consortium. Non-whites accounted for 31.6% of the total participants and 40% of those diagnosed with T2DM. Fewer individuals with diabetes reported being regular smokers than their non-diabetic counterparts (40.3% vs 47.4%). Over 85% of those with diabetes were reported as either overweight or obese at baseline, compared with 60.7% of those without T2DM. We observed differences in all-cause mortality, overall and by T2DM status, between cohorts. FUTURE PLANS: Given the wide variation in demographics and all-cause mortality in the cohorts, MULTITUDE consortium will be a unique resource for conducting research to determine: differences in the incidence and progression of T2DM; sequence of events or biomarkers prior to T2DM diagnosis; disease progression from T2DM to disease-related outcomes, complications and premature mortality; and to assess race/ethnicity differences in the above associations.

Clinical depression and anxiety among ST-elevation myocardial infarction hospitalizations: Results from Nationwide Inpatient Sample 2004-2013.

Depression and anxiety are common among patients who have a major cardiovascular event. However, despite their frequency, there is a lack of evidence regarding the relationship between depression and/or anxiety and receiving revascularization in ST-elevation myocardial infarction (STEMI) hospitalizations. Using data from the Nationwide Inpatient Sample (NIS) from the years 2004 to 2013, we assessed whether a clinical co-diagnosis of depression and/or anxiety decreases the likelihood of revascularization among STEMI hospitalizations. Our central finding is that, paradoxically, the odds of in-hospital mortality were lower among STEMI hospitalizations with a clinical co-diagnosis of depression and/or anxiety as compared to those without. We further discovered that clinical diagnoses of depression and/or anxiety were less prevalent among revascularized as compared to non-revascularized STEMI hospitalizations. However, the percentage of clinical diagnoses of depression and/or anxiety among STEMI hospitalizations increased at a similar rate over a 10-year period irrespective of revascularization status. In conclusion, these results are suggestive of the potentially underdiagnosed mental health issues surrounding major cardiovascular events, and indeed, chronic disease as a whole. To our knowledge, this is the first study to document and examine the "depression paradox" among a population of cardiac patients.

Sex Differences in Early Cardiovascular and All-Cause Hospitalization Outcomes After Surviving Firearm Injury.

The majority of the burden of firearm injury in the United States is on men as compared to women. There is limited evidence regarding sex differences in short-term hospitalization outcomes after surviving firearm injury. The risk of cardiovascular and all-cause hospital readmission, length of stay (LOS), and costs within 180 days after surviving an index firearm injury was compared between males and females. A claims-based, retrospective, cohort study was performed using Nationwide Readmission Database (2013-2014) to obtain a cohort of patients who survived an index hospitalization of firearm injury. The analysis was performed in August 2017. Cox proportional hazard regression models were used to estimate hazard ratio (HR) and 95% confidence intervals (95% CIs). Among 17,594 males and 2,289 females discharged alive after index firearm injury hospitalization, 14.4% and 13.2% were readmitted within 180 days. Within 180 days, the risk of cardiovascular readmission was 3.3 times greater among males versus females (HR = 3.34, 95% CI [1.18, 9.44]. Risk of all-cause readmission among males was greater at 90 days (HR = 1.40, 95% CI [1.04, 1.87]. Patients surviving a firearm injury have a substantial risk of subsequent hospitalizations. Cardiovascular readmissions are greater among males than females during the first 6 months after injury and may be indicative of a continuing long-term risk of health and patient outcomes that contributes to the overall burden of firearm injury.

Adolescent socioeconomic status and depressive symptoms in later life: Evidence from structural equation models.

BACKGROUND: The complex association between socioeconomic status (SES) and depressive symptoms is not entirely understood and the existing literature does not address the relationship between early-life SES and later-life depression from a life-course perspective, incorporating mediating events. METHODS: Using data from the Wisconsin Longitudinal Study, we employed structural equation modeling to examine how SES measured at age 18 affects depressive symptoms at age 54 directly and through mediating variables college graduation, marriage, and household income level at age 36. RESULTS: The total effect of adolescent SES on later-life depressive symptoms is largely mediated through college graduation. Our final model was driven by the effects of women. The variables contributing most to depressive symptoms in women were the direct effect of being raised in a home with a low SES and the indirect effect of low adolescent SES mediated through non-completion of college. LIMITATIONS: Cohort was exclusively comprised of white, high school graduates born in 1939 (± 2 years). In our analysis we assume that missing values are missing at random (MAR); however, attrition both from death (excluded from our population) and from non-response could be associated with depression, i.e. missing not at random (MNAR). CONCLUSIONS: This study demonstrates the impact of completion of college, particularly among women, and supports the social mobility hypothesis to explain the relationship between adolescent socioeconomic circumstances and late-life health.

Genome-wide RNAi Screen for Fat Regulatory Genes in C. elegans Identifies a Proteostasis-AMPK Axis Critical for Starvation Survival.

Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans to identify fat regulatory genes indispensable for starvation resistance. Here, we show that opposing proteostasis pathways are principal determinants of starvation survival. Reduced function of cytoplasmic aminoacyl tRNA synthetases (ARS genes) increases fat mass and extends starvation survival, whereas reduced proteasomal function reduces fat and starvation survival. These opposing pathways converge on AMP-activated protein kinase (AMPK) as the critical effector of starvation defenses. Extended starvation survival in ARS deficiency is dependent upon increased proteasome-mediated activation of AMPK. When the proteasome is inhibited, neither starvation nor ARS deficiency can fully activate AMPK, leading to greatly diminished starvation survival. Thus, activity of the proteasome and AMPK are mechanistically linked and highly correlated with starvation resistance. Conversely, aberrant activation of the proteostasis-AMPK axis during nutritional excess may have implications for obesity and cardiometabolic diseases.

Biochemical and high throughput microscopic assessment of fat mass in Caenorhabditis elegans.

The nematode C. elegans has emerged as an important model for the study of conserved genetic pathways regulating fat metabolism as it relates to human obesity and its associated pathologies. Several previous methodologies developed for the visualization of C. elegans triglyceride-rich fat stores have proven to be erroneous, highlighting cellular compartments other than lipid droplets. Other methods require specialized equipment, are time-consuming, or yield inconsistent results. We introduce a rapid, reproducible, fixative-based Nile red staining method for the accurate and rapid detection of neutral lipid droplets in C. elegans. A short fixation step in 40% isopropanol makes animals completely permeable to Nile red, which is then used to stain animals. Spectral properties of this lipophilic dye allow it to strongly and selectively fluoresce in the yellow-green spectrum only when in a lipid-rich environment, but not in more polar environments. Thus, lipid droplets can be visualized on a fluorescent microscope equipped with simple GFP imaging capability after only a brief Nile red staining step in isopropanol. The speed, affordability, and reproducibility of this protocol make it ideally suited for high throughput screens. We also demonstrate a paired method for the biochemical determination of triglycerides and phospholipids using gas chromatography mass-spectrometry. This more rigorous protocol should be used as confirmation of results obtained from the Nile red microscopic lipid determination. We anticipate that these techniques will become new standards in the field of C. elegans metabolic research.

Dynamics of lipid droplet-associated proteins during hormonally stimulated lipolysis in engineered adipocytes: stabilization and lipid droplet binding of adipocyte differentiation-related protein/adipophilin.

In mature adipocytes, triglyceride is stored within lipid droplets, which are coated with the protein perilipin, which functions to regulate lipolysis by controlling lipase access to the droplet in a hormone-regulatable fashion. Adipocyte differentiation-related protein (ADRP) is a widely expressed lipid droplet binding protein that is coexpressed with perilipin in differentiating fat cells but is minimally present in fully differentiated cultured adipocytes. We find that fibroblasts ectopically expressing C/EBPalpha (NIH-C/EBPalpha cells) differentiate into mature adipocytes that simultaneously express perilipin and ADRP. In response to isoproterenol, perilipin is hyperphosphorylated, lipolysis is enhanced, and subsequently, ADRP expression increases coincident with it surrounding intracellular lipid droplets. In the absence of lipolytic stimulation, inhibition of proteasomal activity with MG-132 increased ADRP levels to those of cells treated with 10 mum isoproterenol, but ADRP does not surround the lipid droplet in the absence of lipolytic stimulation. We overexpressed a perilipin A construct in NIH-C/EBPalpha cells where the six serine residues known to be phosphorylated by protein kinase A were changed to alanine (Peri A Delta1-6). These cells show no increase in ADRP expression in response to isoproterenol. We propose that ADRP can replace perilipin on existing lipid droplets or those newly formed as a result of fatty acid reesterification, under dynamic conditions of hormonally stimulated lipolysis, thus preserving lipid droplet morphology/structure.